bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17205: Contractility in Human Induced Pluripotent Stem Cell Derived Cardiomyocytes is Highly Dependent on Stochastic Variability in Myofilament Development
Authors: Hernandez Jonathan , Arora Akul , Ufford Kathryn , Friedline Sabrina , Tong Zhaowen , Liu Allen , Helms Adam S
Published: July 2021

Introduction:
Modeling heart diseases using cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) enables direct study of cellular and molecular mechanisms. However, the variable phenotypes of individual cells has limited the reproducibility of contractile measurements.
We hypothesized
that variability in myofibrillar development in hiPSC-CMs influences the contractile kinetics and could be controlled for by visualizing and quantifying myofilaments
in vitro
.

Methods and Results:
Control hiPSCs were differentiated into cardiomyocytes (hiPSC-CMs) and purified. hiPSC-CMs were replated at day ~25 onto 8.7 kPa polyacrylamide gels containing fluorescent microbeads and micropatterned with fibronectin in 7:1 aspect ratio rectangles (1750 um
2
). Single iPSC-CMs grew into the rectangular shapes and exhibited spontaneous contractions by day 2 of replating. hiPSC-CMs were stained with live-cell actin dye and imaged on day 5-7 for fluorescent bead displacements and actin videos depicting myofilaments. Traction force analysis of bead displacements was performed to calculate whole-cell force vs. time curves at 33 msec temporal resolution. Myofilament area was measured by thresholding a binary mask on the actin live cell images. Myofilament number varied markedly among individual iPSC-CMs. iPSC-CMs with few myofilaments (myofilament area / cell area <30%) developed low force (<400 uN per cell) and were not included in subsequent analyses. Among cells with myofilament area >30%, the mean traction force was 1368±357 uN and the myofilament area demonstrated a linear correlation with maximum force (R
2
=0.19, runs test p=0.8) with slope of 0.8±0.2 uN/um
2
(p=0.002 vs zero slope). Maximum contraction velocity strongly correlated with maximum force (R
2
=0.31, runs test p=0.4) with slope of 3.9±0.9 sec
-1
(p<0.0001 vs zero slope), as did maximum relaxation velocity (R
2
=0.27, runs test p=0.6, slope 4.1+1.0 sec
-1
, p=0.0003 vs zero slope). Similar results were observed in two control cell lines and with two different purification methods.

Conclusion:
Variability in myofilament development is a critical determinant of contractile force and kinetics in individual iPSC-CMs that should be accounted for in iPSC-CM contractile experiments.
Abstract 17209: Impaired Ventricular-Vascular Coupling in Young Adults Born Preterm
Authors: Mulchrone Ashley , Bellofiore Alessandro , Beshish Arij G , Barton Gregory , Shumaker Heather , Francois Christopher J , Eldridge Marlowe W , Goss Kara N , Chesler Naomi C
Published: July 2021

Background:
Preterm birth affects 10% of live births in the United States, often requiring mechanical ventilation and oxygen supplementation. Although a known risk factor for neonatal and childhood pulmonary vascular disease, little is known regarding the long-term impact on the right ventricle (RV). Here, we utilize novel techniques to investigate RV afterload, contractility, and ventricular-vascular coupling (VVC) in young adults born preterm.

Methods:
Adults born premature (n=7; 4; current age 26.7±0.4 years; gestational age 28.6±1.1 weeks) born with very low birth weight (≤1500g) were recruited from the Newborn Lung Project. Control subjects (n=7; 2) from the same birth years were recruited from the general population. All subjects had no known cardiopulmonary disease. Right heart catheterization (RHC) and magnetic resonance imaging (MRI) were performed to assess right ventricular hemodynamics. Asynchronously acquired pressure and volume data (from RHC and MRI, respectively) were used to compute effective arterial elastance (Ea), end-systolic elastance (Ees), and VVC as: [ESP/SV], [(P
max
-ESP)/SV], and [Ees/Ea], respectively, where ESP is the end-systolic pressure, SV is the stroke volume, and P
max
is the maximum isovolumetric pressure estimated from a novel single-beat approach. Results were analyzed via two-sample t-test; p<0.05 was considered significant.

Results:
Preterm subjects had significantly increased Ea, a measure of RV afterload (Figure 1A). No difference Ees, a measure of RV contractility, was evident (Figure 1B), resulting in significantly impaired VVC in preterm subjects (Figure 1C).

Conclusion:
Otherwise healthy young adults born preterm have high resistance-low compliance pulmonary vascular beds with no RV adaptation, resulting in impaired right ventricular-pulmonary vascular coupling. These findings add to the growing literature that preterm birth has profound lifelong consequences that warrant further study.
Abstract 17228: Not So Fast: Ischemic Stroke Risk in Atrial Fibrillation in the Era of New Hypertension Guidelines
Authors: Sharma Esseim , McCauley Brian D , Wu Wen-Chih , Chu Antony F
Published: July 2021

Introduction:
Atrial fibrillation (AF) is the most common cardiac arrhythmia, with an estimated prevalence in the US of up to 6.1 million people in 2014. The CHA
2
DS
2
-VASc score is a widely used tool to help stratify ischemic stroke risk and guide decision-making regarding anticoagulation in AF based on multiple clinical risk factors including a history of hypertension. While the CHA
2
DS
2
-VASc score has been validated using the prior definition of hypertension (≥140/≥90 mmHg), the 2017 ACC/AHA guidelines define hypertension as ≥130/≥80 mmHg. It is unclear what clinical impact this change will have on the use and validity of CHA
2
DS
2
-VASc scoring and risk/benefit of anticoagulation for prevention of thromboembolic stroke. In order to estimate this impact, we performed a statistical analysis of the NHANES III database.

Methods:
The Third National Health and Nutrition Examination Survey (NHANES III), a nationwide probability survey of 39,695 persons conducted from 1988-1994, was used as a representative sample of the general US population. AF was defined as the presence of AF on ECG or the presence of an irregular pulse on physical exam along with the absence of documented sinus rhythm on ECG.

Results:
We identified 278 patients with AF, with a weighted value representing 2.58 million people. Using the prior hypertension guidelines, 181 patients (weighted value 1.07 million) had a CHA
2
DS
2
-VASc score of ≥2 and qualified for anticoagulation. With the new hypertension guidelines, 200 patients qualified for anticoagulation (weighted value 1.33 million). This represents a 10.5% increase in the number of patients with atrial fibrillation requiring anticoagulation (weighted value 250,000).

Conclusions:
Incorporation of the 2017 ACC/AHA hypertension definitions into the CHA
2
DS
2
-VASc score results in a 10.5% increase in patients who would require anticoagulation from a representative sample of the US population (NHANES III). Clinical risk/benefit for CHA
2
DS
2
-VASc scoring and anticoagulation using this definition for hypertension has not been validated. To avoid potentially unnecessary anticoagulation in AF, clinicians should consider using the ≥140/≥90 mmHg definition for hypertension upon which the CHA
2
DS
2
-VASc scoring is validated.
Abstract 17230: Acute Flash Pulmonary Edema Leads to a Spot Diagnosis of Acute Mitral Regurgitation From Impella LP 5 Induced Chordae Rupture: A Success Story!!
Authors: Gorsi Umama , Wong Kenneth , Vitellas Michail
Published: July 2021

Introduction:
Impella devices are used as a temporary mechanical support for cardiogenic shock. Acute Mitral Regurgitation is a very rare complication after Impella placement. We present a case of sub-acute mitral regurgitation 2 days after removal of the Impala in a patient with cardiogenic shock after an acute anterior myocardial infarction.

Case History:
37-year-old male with no significant past medical history was brought to the Emergency Room because of cardiac arrest at home. Patient had prolonged resuscitation time of about 45 minutes. After return of spontaneous circulation 12-lead electrocardiogram EKG showed typical anterior ST segment elevation MI. Right heart cath confirmed reflecting cardiogenic shock. Coronary angiogram revealed near ostial thrombotic occlusion of the LAD which was successfully treated with a drug-eluting stent. For severely reduced LV systolic function and severe cardiogenic shock Impella CP was inserted. Patient had an episode of cardiac arrest post procedure which was successfully resuscitated. On CCU day one we had a concern about positioning of Impella as it was considered to be under papillary muscle and under fluoroscopy and Echocardiogram guidance we attempted to reposition his Impella. Impella was removed on day 3. However all along we had difficulty adequately oxygenating him. His FiO2 was never below 50%. Eventually 2 days after Impella was removed (day 5 of admission) he had severe flash pulmonary edema. We could not oxygenate him on the ventilator on FiO2 of 100%. There was a concern of acute mitral regurgitation. This was confirmed by transthoracic and transesophageal echocardiogram showed flail anterior mitral leaflet P2 A3 likely chordae rupture. The patient was emergently taken to the operating room by cardiothoracic surgeon to undergo successful mitral valve replacement with a mechanical Saint Jude valve. From there patient slowly recovered. Patient was discharged home directly.

Discussion:
From the beginning it was felt that patient’s event is secondary to chordae rupture from the Impella device as the patient has otherwise demonstrated very good recovery post revascularization and therefore mechanical complication of MI would not be expected, also provided this was LAD territory along with the fact that the flail leaflet was not mediated by a papillary muscle rupture.

Conclusion:
It is pertinent to be very careful while repositioning Impella and one should always aim for a fluoroscopic guidance to reposition the device to avoid any damage to the surrounding structure.
Abstract 17236: Regulating Optimal Angiogenesis and Leukocyte Adhesion of Human Endothelial Cells by Gradient Nanopore Substrate
Authors: Hong Soon Jun , Huang Li-Hua
Published: July 2021

Introduction:
Understanding signals in the microenvironment that regulate endothelial cell behavior are important in tissue engineering.

Hypothesis:
Although many studies have examined the cellular effects of nanotopography, no study has investigated the functional regulation of human endothelial cells grown on nano-sized gradient pore substrate.

Methods:
We examined the cellular response of human umbilical vein endothelial cells (HUVECs) by using a gradient nanopore substrate (GPS) with three different types of hole nanopore patterns (HP): which diameters were described in HP1, 120-200 nm; HP2, 200-280 nm; HP3, 280-360 nm.

Results:
Our study revealed that: (1) HUVECs showed highest proliferation and attachment capacity on HP2 (200-280 nm) GPS, (2) HP2 GPS was determined to be the optimal diameter for extending greater angiogenic potential to HUVECs and (3) both HP2 and HP3 GPS significantly decrease leukocyte adhesion compared to Flat. Moreover, expressions of VCL, TLN1, PXN, ITGA2, ITGA6, ITGAV, ITGB3 and ROCK1 in HUVECs cultured on HP2 GPS were significantly greater than that of Flat. Conversely, TLN1, PXN, ROCK 1 and ROCK2 mRNA levels decreased on HP3 GPS compared to those of Flat. Mature tube structures at 24 hours were found in HUVECs stimulated by HP2 GPS. Expressions of angiogenesis related markers (ANGPT1, TIE2 and CXCR4) and endothelial-related marker (vWF) were significantly increased in HUVECs grown on HP2 GPS. The adhesion of peripheral blood mononuclear cells (PBMNCs) to HUVECs stimulated by HP2 and HP3 GPS was significantly reduced compared to those of Flat at 3, 6 and 24 hours after PBMNC seeding.

Conclusions:
Optimal functional regulations of HUVECs were achieved by nanopore substrate with 200-280 nm-sized pores. Our results provide the possibility of applying nanopore interface-based implant devices in the field of cardiovascular regenerative therapy.
Abstract 17240: A Pilot Clinical Trial to Study Racial Differences in Natriuretic Peptide Response to a High-Carbohydrate Challenge
Authors: Patel Nirav , Russell Griffin , Gutierrez Orlando M , Halade Ganesh , Kain Vasundhara , Prabhu Sumanth D , Arora Garima , Wang Thomas J , Arora Pankaj
Published: July 2021

Introduction:
Human genetic studies have shown a greater risk of cardiometabolic disease with genetically lower natriuretic peptide (NP) levels. We have previously shown that blacks have lower NP levels than whites albeit in older individuals, which is partly explained by genetic factors. A high-carbohydrate challenge in young healthy whites was associated with a reduction in N-terminal pro atrial NP (NTproANP) levels, but no data exist in blacks.

Hypothesis:
We hypothesized that 1) the baseline differences in NP levels by race would be evident in young adults with no comorbidities; 2) blacks would have a reduction in NTproANP levels in response to high-carbohydrate challenge similar to whites but the magnitude of change would differ.

Methods:
Healthy self-identified blacks and whites were screened for the presence of laboratory abnormalities. Each eligible participant was provided 3 days of study diet to standardize salt intake. After the dietary intervention, subjects were brought to the clinical research unit for a high-carbohydrate challenge. Venous blood was collected every hour for 8 hours to perform biochemical assays. African ancestry proportions among self-identified blacks were also determined.

Results:
We recruited 56 healthy participants with a mean age of 26 years, 48% female, 54% whites, mean body mass index 26 kg/m
2
, and an average proportion of 90% African ancestry among self-identified blacks. We found that BNP levels were 24% (95% CI 53 to 6) and N-terminal-proB-type NP (NTproBNP) levels were 44% (95% CI 99 to 17) lower in blacks compared with whites. The decrease in NTproANP levels in response to carbohydrate challenge differed by race (p for interaction=0.03). In response to a carbohydrate challenge, blacks had a 24% reduction in the NTproANP levels (p=0.01) vs. a 47% decrease in the NTproANP in whites (p<0.001) (
Figure, Panel A
), with no change in NTproBNP levels in both races (
Figure, Panel B
).

Conclusions:
Blacks have an endogenously suppressed NP system which may be a biologic determinant contributing to racial disparities in cardiometabolic disease. We have shown that high-carbohydrate diet has a differential effect on NP system by race which needs to be considered while individualizing strategies for disease prevention. (
NCT# 03072602
).
Abstract 17265: Comparing Ultrasound Guided and Conventional Method of Venipuncture for Electrophysiological Procedures: A Meta-Analysis
Authors: Joshi Udit , Siddamsetti Sisir , Ranka Sagar , Rawal Harsh , Parekh Jai , Yandrappalli Srikanth , Kodumuri Vamsi
Published: July 2021

Introduction:
There has been steady increase in the number of catheter ablations for the definitive management of atrial fibrillation and it is associated with its own complications with vascular complications being the most common. There are many studies comparing Ultrasound (US) guided versus Conventional Method (CM) of venipuncture for complications as these patients are on therapeutic anticoagulation. We conducted a meta-analysis to look for any difference between the two approaches.

Methods:
PubMed, Medline, EMBASE and Cochrane databases were analyzed from inception to January 2018 for all studies comparing US vs CM for venipuncture in patients undergoing catheter ablation. Four observational studies and one Randomized Controlled Trial (RCT) with 5158 patients were studied for major and minor vascular complications. Major vascular complications included hematoma/major bleeding (more than or equal to BARC2), AV fistula and pseudo aneurysm. Random effect model was used to estimate the odds ratio of dichotomous outcomes Results: Major and minor vascular complications were significantly less with US guided approach as compared to conventional approach {Odds Ratio (OR): 0.36, 95% CI 0.21-0.61, P=0.0002} and {Odds Ratio (OR): 0.30, 95% CI 0.15-0.64, P=0.002} respectively.

Conclusion:
Real time ultrasound use for venipuncture access is safer approach with significantly lesser vascular complications in patients with atrial fibrillation on anticoagulation undergoing catheter ablation.
Abstract 17270: Prognostic Impact of Ventricular Ectopy During the Recovery Phase of Stress Testing: A Meta-Analysis
Authors: Ayub Muhammad T , Khan Muhammad S , Ranka Sagar , Ishaq Muhammad , Khalid Muhammad F , Paz Luis H , Sleiman Jose , Munoz Ezequiel , Siddamsetti Sisir , Golzar Yasmeen
Published: July 2021

Introduction:
Ventricular ectopy after exercise, due to parasympathetic activity, predicts an increased risk of death in population-based cohorts. We sought to examine the composite risk of all cause mortality in patients with premature ventricular contractions (PVCs) in the early recovery phase of stress testing.

Methods:
PubMed, Medline & EMBASE were queried for all English language articles from 1993 to 2017. The primary outcome was incidence of all cause mortality in patients with frequent PVCs during recovery phase (RPV) of stress testing. Frequent PVCs were defined as the presence of seven or more ventricular premature beats/min, frequent ventricular couplets, ventricular bigeminy or trigeminy, or any other form of ventricular tachycardia or ventricular fibrillation. Meta-analysis of the main outcome was performed using a weighted random effects model.

Results:
A total of four observational studies including 38765 patients were retrieved. Data for 2065 patients with RPV was pooled. A comparative analysis of PVC vs Infrequent/Non-PVC group showed a calculated risk ratio for all cause mortality of 1.8 (95% CI 1.36-2.38; p=0.001). I
2
statistic for heterogeneity testing was 82.8% (Fig.1).

Conclusion:
Frequent premature ventricular contractions during early recovery phase of stress testing are associated with increased all cause mortality as compared to patients with infrequent or no PVCs.
Abstract 17281: Esophageal Re-Warming Profile During Cryoballoon Ablation Why We Should Avoid the Freeze Thaw Refreeze Technique
Authors: Tomaiko Emrie D , Orme Joseph , Habib Adnan , Su Wilber , Wang Paul J , Jaskanawal Bisla , Su Stephen
Published: July 2021

Introduction:
Cryoballoon ablation collateral injury such as atrial-esophageal fistula (AEF) has been reported. Dosing regimens such as the Freeze-thaw-refreeze technique are often used; however, the effect on esophageal rewarming profile is not well understood. The goal of this study is to obtain objective evidence supporting the monitoring of esophageal temperature and the avoidance of the freeze-thaw-freeze technique to reduce injury.

Methods:
Thirty patients undergoing cryoballoon ablation had their esophageal temperatures measured throughout the procedure using the Circa S-CathTM. Patients underwent ablation with the 28mm Arctic Front Advance® cryoballoon with dosing times of < 180 seconds. No consecutive ablations were performed. Temperature profiles using the readings from the 12 serial sensors were analyzed. Nadir temperature points were used for analysis of esophageal temperature recovery characteristic. Temperature difference intra-pole and esophageal rewarming time was recorded and compared.

Results:
Successful recording of esophageal temperature was seen in all patients. The average rewarming time on the lowest detected temperature to 35 C recorded. Potential false negative esophageal temperature comparing nadir pole to the neighboring temperature pole was significant (difference in over 10 degrees Celsius) in all recordings. Typical free-thaw-refreeze timing of cryoballoon (1 minute post ablation), would therefore initiate freezing when esophageal temperature are still unrecovered in all of the patients with reduced esophageal temperature.

Conclusions:
Esophageal temperature rewarming characteristic during cryoballoon is not well understood. Further studies are needed to more accurately assess true esophageal temperature, cooling, as well as rewarming characteristics. Consecutive cryoballoon ablation with free-thaw-refreeze technique, prior to complete esophageal rewarming, will likely result in significant esophageal injury.
Abstract 17283: De-Escalation of Antiplatelet Therapy in Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Clinical Trials
Authors: Kheiri Babikir , Osman Mohammed , Abdalla Ahmed , Ahmed Sahar , Osman Khansa , Bachuwa Ghassan , Hassan Mustafa , Bhatt Deepak L
Published: July 2021

Introduction:
Potent P2Y
12
-receptor inhibitors are recommended in the management of acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI). As the risk of thrombotic complications from an ACS event is highest in the early “ischemic phase,” the greatest benefit of potent P2Y
12
blockade occurs early. However, the risk of bleeding from such therapy tends to occur with chronic treatment during the “maintenance phase.” Therefore, a stage-adapted strategy with the early use of potent P2Y
12
blockade in acute treatment, followed by de-escalation to clopidogrel during the maintenance phase is common. Nevertheless, clinical outcomes supporting this strategy are lacking.

Hypothesis:
This study aimed to evaluate the safety and efficacy of antiplatelet de-escalation compared with continuation in patients with ACS treated with PCI.

Methods:
Electronic databases search were conducted for all randomized clinical trials (RCTs) that evaluated the safety and efficacy of antiplatelet de-escalation compared with continuation in patients with ACS treated with PCI. A random-effects model was used to calculate the pooled summary estimates.

Results:
We included 3 RCTs with 3,391 total patients (median follow-up 12 months). The net clinical outcome (composite of thrombotic or bleeding events) was significantly reduced in the switched group compared with the continued group (8.7% vs 12.1%; risk ratio (RR): 0.64; 95% confidence interval (CI): 0.43-0.97; P=0.03). However, there were no significant differences between groups in major adverse cardiovascular events (RR: 0.78; 95% CI: 0.55-1.11; P=0.17), all BARC (Bleeding Academic Research Consortium) types bleeding (RR: 0.61; 95% CI: 0.33-1.11; P=0.10), or BARC types ≥2 bleeding (RR: 0.49; 95% CI: 0.19-1.26; P=0.14).

Conclusions:
Our results suggest a net clinical benefit of de-escalation therapy shortly after PCI in ACS patients, without increased risk of MACE or bleeding, though further adequately powered trials are needed to confirm this finding.
Abstract 17284: Clinical Characteristics and Management of Patients With Heart Failure With Mid-Range Ejection Fraction: A Systematic Review and Meta-Analysis
Authors: Godoy Rivas Carlos A , Urrutia Samuel , Montalvan Eleazar , Rodriguez Mario , Venegas Eduardo , Simonson Marian , Gorodeski Eiran , Ayoub Chadi G , Ahmed Haitham G
Published: July 2021

Introduction:
Heart Failure (HF) is categorized according to the AHA/ACC 2013 HF Guidelines based on Left Ventricular Ejection Fraction (LVEF); HF with Reduced Ejection Fraction (HFrEF, EF≤40%), and HF with preserved EF (HFpEF, EF ≥ 50%). There is a group of “borderline” patients with EF 41%-49%, termed Heart Failure with Mid-Range Ejection Fraction (HFmrEF). Given this category is not well understood, we sought to evaluate clinical characteristics and management patterns for patients with HFmrEF.

Methods:
A systematic review was performed using Ovid MEDLINE, EMBASE, Cochrane CENTRAL and LILACS (1946 – 03/2018). Search terms included HF, mid-range, borderline LVEF with several ranges (40-50 or 40-45 or 45-50). Variables characterizing clinical features and medications were extracted for each HF group and adjusted odds ratios (ORs) were pooled.

Results:
Of 1,131 abstracts identified, 24 met inclusion criteria (total patients 480,188). Patients with HFmrEF compared to those with HFrEF were more likely to be female (OR 1.42), have hypertension [HTN] (OR 1.34) and diabetes (OR 1.11), higher SBP (OR 1.17), better NYHA-FC (FC I OR 1.73, FC II 1.33), less likely to have coronary artery disease [CAD] (OR 0.74) and more likely to be treated with ACEI, ARB, BB, Digoxin, MRA and statins (Figure 1-2). HFmrEF patients when compared to those with HFpEF were less likely to be female (OR 0.54) or have HTN (OR 0.68), and more likely to have CAD (OR 1.25), and to be treated with HF medications and statins.

Conclusions:
Patients with HFmrEF have higher SBP and better NYHA-FC (I and II) compared to HFrEF patients and are less likely to be female and more likely to have CAD compared to HFpEF patients. Further research is needed to help guide management in this unique but clinically important population.

Figure 1A. Forest plot of adjusted ORs comparing baseline clinical characteristics of HFrEF vs HFmrEF patients

Figure 1B. Forest plot of adjusted ORs comparing baseline clinical characteristics of HFmrEF vs HFpEF patients

Figure 2A. Forest plot of adjusted ORs comparing medications used in HFrEF vs HFmrEF patients

Figure 2B. Forest plot of adjusted ORs comparing medications used in HFmrEF vs HFpEF patients
Abstract 17285: Trends and Outcomes of Fibrinolytic Therapy in Patients With Pulmonary Embolism and Metastatic Cancer
Authors: Ogunbayo Gbolahan O , Pecha Robert , Misumida Naoki , Ayoub Karam , Hillerson Dustin , Abdel-latif Ahmed , Elayi Claude S , Messerli Adrian W , Smyth Susan S
Published: July 2021

Introduction:
Pulmonary embolism in the setting of cancer portends a poor prognosis. There is limited data on the use and outcomes of fibrinolytic therapy (FT) in this subgroup of patients. This study describes temporal trends and outcomes of the use of FT among these patients.

Hypothesis:
The use of FT in patients with metastatic cancer and acute pulmonary embolism is associated with higher mortality

Methods:
Using the NIS database, we extracted patients with metastatic cancer admitted with a primary diagnosis of acute pulmonary embolism from January 2010 to December 2014. Using weighted data we analyzed the trends of FT in these patients. For analysis of outcomes, we performed a propensity score matching (match tolerance.01) of patients with PE and FT. After matching, we compared baseline characteristics and inpatient outcomes of patients with PE who underwent FT with those that did not. Or primary outcome was mortality. We performed a multivariable regression analysis with mortality as our outcome. We also described predictors of mortality in patients that underwent FT.

Results:
Of the 65,882 patients with metastatic cancer admitted with a primary diagnosis of PE, 946 (1.4%) underwent fibrinolytic therapy. There was a significant trends of increase in the use of FT in this cohort of patients, increasing from 0.9% in 2010 to 2.1% in 2014. After exclusions 666 were included in the propensity match and all were matched. Both groups were well matched with regards to baseline characteristics. Patients with FT were less likely to be Caucasian or have anemia. The use of FT was more common in teaching hospitals. Patients in the FT arm were more likely to have cardiac arrest, respiratory failure and acute renal failure. There was no difference in rates of bleeding or blood transfusion. Mortality was significantly higher in the FT arm (24% vs. 1.6%, p<.01). In multivariable analysis, FT was independently associated with mortality (OR 8.35, 95% CI 2.2-32.94; p<.01). Among patients with metastatic cancer and acute PE that underwent FT, independent predictors of mortality were Obesity (OR 4.51, 95% CI 1.35-15.03; p=.02), history of coagulopathy (OR 6.71, 95% CI 1.35-33.46; p=.02), current tobacco abuse (OR 3.26, 95% CI 1.04-10.21; p=.04) and a history of anticoagulant use (OR 2.21, 95% CI 1.02-4.82; p=.046).

Conclusions:
Fibrinolytic therapy in patients with metastatic cancer and acute pulmonary embolism is associated with increase mortality. The clinical benefits expected from the use fibrinolytic therapy in these patients should be weighed against the risks.
Abstract 17293: Functional Outcomes After Acute Pulmonary Embolism
Authors: Brailovsky Yevgeniy , Kunchakarra Siri , Porcaro Katerina , Doukas Demetrios , Stiff Andrew , Bechara Carlos , Lopez John , Mathew Verghese , Fareed Jawed , Darki Amir
Published: July 2021

Introduction:
Pulmonary embolism (PE) is associated with significant acute morbidity, mortality, and long term functional limitations. There is paucity of data on acute and short term functional assessment after acute PE.

Hypothesis:
Functional capacity will improve from baseline to follow up among patients with acute PE.

Methods:
We prospectively analyzed patients who underwent evaluation by the pulmonary embolism response team (PERT) at Loyola University Medical Center between 2016 and 2018. We included patients with acute PE who underwent six-minute walk test (6MWT) at discharge and during outpatient follow up (50±72 days post discharge). We collected demographic and clinical characteristics. We used paired sampled t-test to compare continuous variables.

Results:
Among the 204 patients evaluated by PERT, 38 patients (18.6%) underwent 6MWT at baseline and follow up. Patients were classified as low risk (6 patients), submassive (29 patients), and massive (3 patients). Mean age was 61.3±14.2, 50% were female, 60.5% were white, 26.3% were black, 29% had cancer, and 68.4% had concomitant DVT, mean BMI 36.4±10.3, and mean PESI score was 96.8+44.4. Overall the mean 6MWT distance increased significantly from a baseline of 726.9±73.7 feet to 1042±72.8 feet at follow up (p<0.001). Low risk (786±204 to 1115.8+177.6 p=0.63), Submassive (700.2±85 to 995.6±82.8 p<0.001), and Massive PE (859±261.7 to 1343.3±307 p=0.168) groups all demonstrated improvement in 6MWT distance.

Conclusions:
Functional capacity as measured by 6MWT significantly improved during follow up after acute PE. Future studies are needed to determine predictors of favorable functional outcome and best treatment strategies.
Abstract 17294: The Effect of Statewide Electronic Reporting on Pulse Oximetry Screening in Newborns
Authors: Engel Melissa , Phimister Ashley , Gaviglio Amy , Spector Logan , Lohr Jamie L
Published: July 2021

Background:
Pulse oximetry screening (POxS) is used to screen newborns for critical congenital heart disease (CCHD). A pilot study in Minnesota identified missed screens in eligible newborns and incorrect interpretation of the screening algorithm as major barriers in our screening program. To address these issues, the Minnesota Department of Health (MDH) implemented a statewide electronic reporting system for POxS with clinical decision support (MNScreen). MNScreen records individual POxS data at testing and provides real-time clinical decision support at bedside. This system has been utilized in all birth hospitals, birth centers, and by many midwives in Minnesota since January 1, 2017.

Objective:
Our goal was to determine the impact of MNScreen on missed and misinterpreted POxS in its first year of use. Subsequent work will be aimed at determining if MNScreen improves POxS detection of CCHD. No prior assessment of statewide electronic screening programs has been reported.

Methods:
Retrospective analysis of the statewide POxS data for all infants born in Minnesota and reported via MNScreen in 2017. MNScreen data was compared to state birth records to assess completeness of screening. Data was analyzed for positive screens and accurate interpretation of POxS algorithm.

Results:
POxS was performed on 65,018 (96.4%) of eligible newborns in 2017. A positive screen was accurately reported in 124 newborns (0.19%). POxS was misinterpreted at reporting in 284 (0.44%) of newborns, despite clinical decision support. Overall, POxS rates improved when compared to 10.7% of missed screens in the pilot study. The rate of misinterpreted screens remained high in year 1 of MNScreen (0.44% vs 0.29% in pilot).

Conclusions:
Missed POxS and misinterpretation of POxS algorithms are a major challenge for CCHD screening programs. In the first year of MNScreen, the percentage of newborns screened improved, but the accuracy of algorithm interpretation did not, despite cues from the automated screening software. Real time data transmission allows rapid MDH follow up of at risk newborns. Further work will include identifying strategies to reduce missed screens and making Improvements to the MNScreen software to reflect on-site POxS decision making.
Abstract 17297: Comparative Analysis Between Coronary Angiotomography and Sensitive Troponin in Chest Pain With Intermediate Risk of Acute Coronary Syndrome: Conecttin Trial
Authors: Soeiro Alexandre d , Biselli Bruno , Leal Tatiana C , Bossa Aline S , César Maria C , Jallad Sérgio D , Serrano Carlos V , Nomura Cesar H , Nakamura Débora , Rochitte Carlos E , Oliveira Múcio T
Published: July 2021

Introduction:
Various questions about methods of diagnosis still remain obscure and there is no effective comparison between them in patients with intermediate risk.

Hypothesis:
Coronary computed tomography angiopraphy (CCTA) is better than troponins in the detection of coronary artery disease in patients with chest pain and the intermediate probability of acute coronary syndromes (ACS).

Methods:
Were included prospectively 100 patients with chest pain and TIMI risk score 3 or 4. All patients were submitted to troponin measurements and CCTA. If CCTA showed coronary stenosis ≥ 50%, patient was initiate the ACS treatment and was hospitalized to have coronary cineangiography. If CCTA shows lesions < 50%, the patient was discharged and monitored for 30 days. A second sampling of the troponin was obtained (blinded) from all patients three hours after the first collection. Significant coronary lesion was considered when ≥ 70%. The kit of troponin ADVIA Centaur® TnI-Ultra (Siemens Healthcare Diagnostics, Tarrytown, NY, USA) was used. The CCTA used was the 320-channel Toshiba Aquilium machine. The comparison between methods was performed through the Kappa agreement analysis. Were calculated sensitivity, specificity, and negative and positive predictive values between the sensitivity troponin versus CCTA in the detection of an ACS. Complementary analysis was made by ROC curve calculating the area under the curve (AUC) and the cut-off score of troponin and coronary lesions on angiography/events. Combined events after 30 days were: hospitalization, death and myocardial infarction.

Results:
The Kappa agreement analysis between troponin and CCTA in the detection of coronary lesions showed low correlation (kappa = 0.022,
p
= 0.78). Thirty eight (38%) patients were subjected to angiography and significant coronary injury was confirmed at 81.6%. In 62 patients with CCTA lesions < 50%, 2 (3.2%) events were observed in 30 days. Area under the troponin curve related to the presence of significant coronary lesions was 0.401 (IC 95%: 0.156 - 0.646), related to events was 0.808 (IC 95%: 0.695 - 0.922) and related to coronary lesions or events was 0.547 (IC 95%: 0.428 - 0.667). The best percentage variation cutting points of troponin were 20% (sensitivity = 32.3% and specificity = 71%) and 27.5% (sensitivity = 50% and specificity = 75%), respectively related to significant coronary lesions and events.

Conclusion:
The use of CCTA in patients with intermediate risk for ACS proved to be safe and superior to the sensitive troponin in the detection of coronary heart disease.
Abstract 17298: Body Awareness but Not Interoceptive Awareness is Associated With Better Heart Failure Self-Management
Authors: Vehovec Anton , Dolansky Mary , Josephson Richard , Hughes Joel
Published: July 2021

Introduction:
Self-management is important for individuals with heart failure HF to prevent the worsening of the disease and improve quality of life. Self-management includes maintenance, symptom perception, and symptom management. Interoception which includes interoceptive awareness and body awareness are possible mechanisms to explain why patients with HF struggle with self-management. Interoceptive awareness is the objective ability to feel visceral stimuli and use it to inform a decision. Body awareness is the subjective rating of their ability to feel and understand their body. The purpose of this cross sectional descriptive study was to determine if there is an association between interoception and HF self-management and if there are moderating effects of influencing factors on the relationships between interoception and HF self-management.

Methods:
A total of 100 individuals with heart failure were recruited from a heart failure clinic. Participants answered questionnaires, completed a cognitive test, and the heart beat perception task. Multivariate linear regression was used to test the effect of interoception variables on self-management variables while controlling for anxiety, depression, attention, comorbidities, and rumination. Moderation models for each combination of interoception variables and influencing factors for each outcome were tested.

Results:
The only significant effect between interoception on a self-management variable was between body awareness and symptom perception (b=.162, p<.05). There were only two significance moderation models. The first was body awareness and comorbidities on symptom management where there was only a positive significant effect of body awareness on symptom management at low values of comorbidities (<2.63). The second moderation model was body awareness and attention on symptom management where there was only a positive significant model at high levels of attention (>90.4).

Conclusion:
Interoceptive awareness did not have a significant moderation model on any self-management variables. Higher body awareness is significantly associated with better maintenance and symptom management.
Abstract 17311: Gut Microbiota Derived Metabolites Impact Lymphatic Inflammatory Mechanisms
Authors: Lopez-Gelston Catalina , Eshghjoo Sahar , Weeks Cassidy , DeLeonibus Sabrina , Jayaraman Arul , Alaniz Robert C , Chakraborty Sanjukta
Published: July 2021

Diet induced changes in gut microbial composition and dysregulated immune responses are key players in the progression of metabolic syndrome (MetSyn) and obesity.The lymphatics that are directly exposed to the gut microbiota in the mesenteric bed are central players in inflammatory and immune responses and are impaired during MetSyn. However, the mechanisms remain unknown.Endogenous tryptophan derived gut microbiota metabolites such as indole, significantly limits inflammation and immune response. We hypothesize that microbiota influence the lymphatic mesenteric microenvironment via such discrete metabolites to impact metabolic disease. We evaluated the effects of indole, tryptamine and indole-3-acetate (I-3A) on inflammatory mechanisms in vitro and in vivo using cultured models of lymphatic endothelium (HDLECs) and rat models of high fructose diet induced MetSyn and LPS induced acute inflammation. HDLECs were treated with varying doses of indole, tryptamine and I-3A (100uM-500uM) in presence or absence of LPS (20ng/ml) and its effects on inflammatory cytokines were evaluated. Rats were injected with LPS (10mg/kg, 24hrs) with or without indole (20mg/kg) to assess for inflammation. Further, rats were also subjected to a 7-week high fructose (60%) diet regimen and gavaged with indole for 4 weeks prior to completion of the diet regimen and metabolic parameters were measured. Our results show that indole decreases levels of inflammatory cytokines as cfos, cjun, IL1β, MCP1, JAK1, SOCS3 and SOCS1 induced by LPS in the HDLECs and in the mesenteric arcades and lymph nodes. Similar effects are also observed with tryptamine and I-3A. Flow cytometric analysis of tissues show that indole significantly suppresses the population of inflammatory MHCII
+
/cd45
+
cd11b
+
cells (p<0.02) and augments Foxp3+/cd4+ cells (p<0.003) in the mesenteric arcades, lymph nodes and spleen that are induced in LPS treated animals. In MetSyn animals, indole reduces levels of glucose, triglyceride and epididymal fat content that is also associated with concomitant decrease in expression of inflammatory cytokines. Taken together, we show that indole and other tryptophan metabolites limit lymphatic inflammatory pathways and also decreases metabolic parameters associated with MetSyn and thus can be a viable therapeutic intervention for metabolic disease.
Abstract 17353: Comparing the Association of DKK-1, a Wingless (Wnt)-Regulatory Molecule, and CRP-1 With Cardiovascular Risk Factor Profile and Coronary Plaque Burden in Patients With Coronary Artery Disease
Authors: Dao Benjamin , Elbebabawy Bishoy , Sayid Ibrahim , Kandala Jagdesh , Rammohan Harish Raj Seetha , Katz Daniel , Jenkins Paul , Gadomski Anne , Hyink Deborah , Klotman Paul , Hutter Randolph
Published: July 2021

Introduction:
Our group has shown the Wnt-pathway to be a key regulator of SMC function and to be expressed in human coronary atheroma. Dickkopf-related protein 1 (DKK-1) is a member of the Wingless (Wnt) signaling pathway molecules and has recently been shown to improve GRACIE-risk factor score prediction of coronary events in chest pain patients and to predict restenosis post coronary stenting. We tested its association with coronary plaque burden and cardiovascular risk factors in comparison with CRP-1;

Hypothesis:
DKK-1 may be associated with coronary artery plaque burden and cardiovascular risk factors and play a role in coronary artery disease through modulation of SMC.

Methods:
218 patients with angiographic evidence of CAD (mildly obstructive CAD, n=35; obstructive stable CAD, n=154; unstable CAD, n=29) were enrolled in this study at the time of cardiac catherization. DKK-1 and CRP-1 were measured by ELISA. Data are shown as Mean p SEM. Values of DKK-1 and CRP1 were skewed, so non-parametric tests were used to determine the associations between DKK-1 and CRP-1 with Syntax Score, age, BMI, LDL, HDL, and HgbA1c. . Spearman’s Rank Order Correlation, Wilcoxon Rank Sum Test, and analysis of variance (ANOVA) were used to assess associations.

Results:
Data are shown as Mean p SEM.Variables were as follows: DKK-1 736 pg/ml p 129, CRP-1 0.108 mg/ml p 0.01, age 66 years p 1, BMI 32 p 0.5, LDL 97 p 3, HDL 46 p 2, HgbA1C 6.5 p 0.2, Syntax score 11 p 0.7. With DKK-1 the only statistically significant correlation observed was between DKK-1 and HgbA1c (r=0.18, P<0.05). There was no association between DKK-1 and CRP-1, Syntax Score, Age, BMI, LDL, and HDL. With CRP-1, however, we observed significant positive correlations with Syntax Score (r=0.2, P<0.05), BMI (r=0.18, P<0.05), LDL (r=0.18, P<0.05) and significant negative correlation with age (r= -0.19, P<0.05) and with HDL (r=-0.18, P<0.05). There was no association between CRP-1 and HDL as well as HgbA1c.

Conclusions:
In patients with angiographically established CAD DKK-1 in contrast to CRP-1 is not a predictor of coronary plaque burden and has as only significant association a positive correlation with HgbA1c. Our data suggest that the reported role of DKK-1 in coronary event risk and in restenosis might be related to Diabetes mediated effects.
Abstract 17363: Inter-Individual Heterogeneity Among Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Response to Kinase Inhibitors
Authors: White Matthew C , Aggarwal Praful , Matter Andrea , Turner Amy , Mattes William B , Broeckel Ulrich
Published: July 2021

Introduction:
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide unprecedented opportunities for novel investigations into the impact of individual heterogeneity on drug response. Cardio-oncology is a field of growing clinical importance due to the significant, but often sporadic, incidence of cardiotoxicity among cancer patients, including those receiving targeted therapeutics such as kinase inhibitors (KIs). Current commercially-available hiPSC-CMs are typically derived from single donors, and thus do not capture the inherent heterogeneity of patient populations.

Hypothesis:
We hypothesized that hiPSC-CMs derived from different individuals would display heterogeneous sensitivities to KIs.

Methods:
We tested iPSC-CMs from six individual participants as part of the NHLBI HyperGEN cohort. Cells were plated on 96-well ePlates (ACEA Biosciences, San Diego, CA) per manufacturer’s instructions and allowed to mature for 10-14 days prior to use. Four KIs were tested (sunitinib, vandetanib, nilotinib, and gefitinib) at concentrations ranging from Cmax to 30-fold Cmax. Toxicity was assessed using non-invasive impedance-based endpoints (beating rate, beat amplitude, and cell index) and ATP levels (Promega, Madison, WI).

Results:
We observed differences in baseline beating rates (BRs) among the hiPSC-CMs despite similar morphology and cardiac troponin expression levels. Following drug exposure, cell-line and drug- dependent differences in BR and cell index/viability (CI) became apparent. For example, the relatively non-cardiotoxic KI gefitinib produced few significant changes in BR or CI across all 6 cell lines, whereas KIs with black-box warnings for cardiotoxicity severely impacted these endpoints. For both vandetanib and nilotinib, statistically significant differences (p ≤ 0.05) in BR were observed between multiple cell lines at 24 hours post-exposure. Furthermore, nilotinib induced significant differences (p ≤ 0.05) in CI between multiple cell lines after 24 hours.

Conclusions:
Taken together, these results strongly suggest that inter-individual differences impact hiPSC-CM cardiotoxicity assessments, and support the need to test multiple cell lines during in vitro toxicity screens.
Abstract 17376: Risk of Early Reablation Post Cryoballoon Ablation
Authors: Tomaiko Emrie , Habib Adnan , Orme Geoffrey J , Su Wilber
Published: July 2021

Introduction:
Post-ablation radiofrequency tissue friability has been described; however, tissue friability post cryoablation has not been well studied. We report a case of left atrial perforation with normal contact force radiofrequency ablation 22 days after initial cryoballoon ablation.

Description:
A 59-year-old male with persistent atrial fibrillation, severe biatrial enlargement, non-ischemic cardiomyopathy (EF of 20%), underwent initial cryoballoon pulmonary vein isolation with left atrial roof cryoablation with restoration of sinus rhythm and no complications. Patient presented 22 days later with sustained atrial flutter and heart rate over 130 bpm refractory to aggressive medical management, cardioversion, and acute on chronic congestive heart failure. Early re-ablation was performed with electrophysiology study and 3D activation map confirming ectopic atrial tachycardia foci arising from left atrial roof, anterior to the border of previously cryo-ablated region. St. Jude TactiCath™ contact force ablation catheter, was used to ablate this foci, and termination within 5 seconds of ablation was observed. Using the Force-Time Integral index to guide further ablation, the surrounding area was ablated for an additional 20 seconds at 30 W with a maximum recorded contact force throughout the procedure of 35 grams, and an average of 10-15 grams.A decrease in systolic blood pressure from 120 mmHg to 80 mmHg was noted, and intracardiac ultrasound confirmed 1.5 cm of pericardial effusion. Successful pericardiocentesis and reversal of anticoagulation was performed with ongoing bleeding, and eventual surgical intervention was required. On direct visualization during surgery, the left atrial roof perforation was confirmed, and was noted to be very friable and difficult to retain suture for repair. Patient did well post-operatively and was discharged with no recurrence of arrhythmias.

Conclusions:
Despite standard of care monitoring, including force-time integral index and contact-sensing catheters, atrial perforation occurred likely due to increased tissue friability post initial cryoablation. The optimal timing for repeat ablation is not completely understood, and extreme caution and avoidance of early re-ablation risk is prudent.