bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16900: Exertional Hemodynamics Among Patients With HFrEF Based on Resting HF Profile
Authors: Buchanan Cole , Pratt-Cordova Ashley , Coe Gregory , Allen Larry A , Wolfel Eugene E , Cornwell William K
Published: May 2021

Introduction:
HFrEF can be classified by profiles A, B, C or L based on resting pulmonary capillary wedge pressure (PCWP) and cardiac output (Qc). We characterized exertional hemodynamics by HF profile.

Methods:
HFrEF patients (N=34) completed invasive exercise testing with Swan-Ganz and radial arterial catheterization on upright bicycle. Oxygen uptake was monitored by indirect calorimetry. Data were recorded at supine and upright rest, two exercise stages below ventilatory threshold (steady states 1 and 2), and peak exercise. Participants were stratified into HF profiles based on supine resting hemodynamics including PCWP and cardiac index (CI): Profile A (warm-dry) PCWP≤16mmHg, CI≥2.5L/min/m
2
; Profile B (warm-wet) PCWP>16mmHg; CI≥2.5L/min/m
2
; Profile C (cold-wet) PCWP>16mmHg; CI<2.5L/min/m
2
; Profile L (cold-dry) PCWP≤16mmHg, CI<2.5L/min/m
2
.

Results:
Demographics are displayed in the
table
. Peak oxygen uptake (VO
2
) was severely reduced in all participants (
figure 1
). Throughout exercise, profile C and L patients had lower stroke volume and Qc, but higher (A-V)O2 difference than profiles A and B (
figure 2
). Profile B and C patients had higher resting and exertional pulmonary arterial and PCWP filling pressures compared to profiles A and L.

Conclusion:
Exercise performance among HFrEF patients is not uniform. Exertional hemodynamics vary substantially based on HF profile.
Abstract 16907: Relationship Between 3
rd
Trimester Umbilical Arterial Blood Flow and Neurodevelopmental Outcomes at 2 Years in Major Fetal Heart Disease
Authors: MORAY AMOL , robertson charlene , Bond Gwen , Abeysekera Jayani , Mohammadian Parsa , Dinu Irina , Atallah Joseph , Hornberger Lisa K
Published: May 2021

Introduction:
Congenital heart disease (CHD) requiring surgical intervention in infancy is associated with impaired neurodevelopmental (ND) outcomes which may be due in part to prenatal insults. Supporting this, we recently found an inverse relationship between 3
rd
trimester umbilical artery Doppler-based (UA) pulsatility index (PI=systolic velocity-diastolic velocity/mean velocity) and growth and ND outcomes at 2 years in hypoplastic left heart syndrome and d-transposition of great arteries. In the present study we explore associations between 2
nd
and 3
rd
trimester UA-PI in all major fetal CHD and 2-year ND outcomes.

Methods:
We identified all patients with major structural CHD and fetal echocardiography who underwent cardiac surgery and 2-year ND and biometric assessments (Western Canadian Complex Pediatric Therapies Follow-up Program) from 2007-2017 in our program. Eligible surgeries were: bypass
<
6 weeks, shunts at
<
6 months or isomerisms with surgery at
<
12 months. Patients with genetic syndromes were excluded. 2
nd
and 3
rd
trimester UA-PI z scores were examined for relationships with 2 year Bayley III ND scales. Data is presented as mean (SD).

Results:
Data from 147 children was analysed (see Table). 2
nd
and 3
rd
trimester fetal echo was performed at 22.4(3.7) and 34.7(2.9) weeks, with UA-PI z scores of 0.18 (0.3), and 0.51(1.4) and respectively. The Bayley III cognitive, language and motor scores were 93(13), 89(15) and 89(14) for the entire group. Multivariable regression analysis of the entire group and specific subgroups showed an inverse relationship between 3
rd
trimester UA-PI and ND domains (see Table). No association was found for 2
nd
trimester UA-PI and ND for the whole group and subgroups.

Conclusions:
Increased 3
rd
trimester UA-PI, which could reflect an altered late gestation placental circulation, inversely relates to abnormal 2 year ND. These relationships are most notably observed in SVs and in CHD associated with AOTO.
Abstract 16912: Cardiac Microstructural Associations With Pulse Pressure Differ by Sex
Authors: Salto Gerran , Kwan Alan C , Osypiuk Ewa , Stantchev Plamen , Kim Elizabeth H , Hiremath Pranoti , Cheng Susan
Published: May 2021

Background:
Alterations in the orientation and integrity of myocardial fibers can be assessed using ultrasonic image analysis. The ability to detect such microstructural abnormalities may shed light on sex differences in the progression from common risk factors, such as blood pressure elevation, to overt cardiac disease.

Methods:
In a community-based cohort of N=2510 adults (age 66±9 years, 56% women) without overt cardiovascular disease, we evaluated whether a novel echocardiography-based assessment of left ventricular myocardial microstructure, the signal intensity coefficient (SIC), could detect tissue-level alterations that are associated with blood pressure parameters including pulse pressure, an indirect measure of large artery stiffness and established correlate of adverse cardiac outcomes.

Results:
We observed that for every 10 mmHg increase in pulse pressure, women had a significantly greater degree of cardiac microstructural alteration (coeff 0.07; s.e. 0.02, P<0.001), whereas this age-adjusted association was not seen in men (coeff -0.01; s.e. 0.02, P=0.65) (

Figure

). Although we observed similar results for systolic, diastolic, and mean arterial pressure, the sex interaction terms were non-significant (P>0.05) for these other parameters.

Conclusion:
A novel index of myocardial tissue alteration is associated with incremental elevations in pulse pressure in women but not in men. Further research is needed to examine the extent to which cardiac microstructural abnormalities may mediate the risks for cardiac disease in women, particularly those conditions involving large artery stiffening such as heart failure with preserved ejection fraction.
Abstract 16916: Asymptomatic Patients With Duchenne Muscular Dystrophy Have Elevated Troponin
Authors: Sheybani Aryaz , CRUM Kim , Raucci Frank J , Markham Larry W , Soslow Jonathan H
Published: May 2021

Introduction:
Cardiomyopathy is the leading cause of death in Duchenne Muscular Dystrophy (DMD), but traditional heart failure biomarkers have limited utility. Cardiac Troponin I (cTnI) has been used in DMD research studies as a marker of toxicity, but little is known about cTnI levels in asymptomatic patients. The goal of this study was to longitudinally evaluate cTnI, NTproBNP, and BNP in an asymptomatic DMD cohort. We hypothesized the biomarkers would not correlate with cardiac function, but some asymptomatic patients would exhibit a cTnI leak, reflecting ongoing myocardial inflammation related to disease progression.

Methods:
Asymptomatic DMD patients (N=69) and controls with normal cardiac evaluations (N=18) were enrolled. In DMD subjects, biomarker levels were obtained at time of cardiac magnetic resonance imaging (CMR), which included assessment of atrial and ventricular volumes, function, and late gadolinium enhancement (LGE). Normal ranges for biomarkers were created based on control values. Spearman correlation was used for analysis.

Results:
There was no consistent correlation between biomarkers and disease progression by CMR (Table 1). Several DMD subjects had transiently elevated cTnI (Fig 1). Those with elevated cTnI trended towards being more likely to have LGE on baseline CMR, though this did not reach statistical significance (p= 0.08).

Conclusions:
CTnI, BNP, and NTproBNP do not correlate with CMR assessment of cardiomyopathy progression. There is a subset of the DMD cohort with asymptomatic cTnI leak. While this cTnI leak is of uncertain clinical significance, it is important to recognize if cTnI is used to assess for cardiac toxicity in future drug trials.
Abstract 16918: COVID-19 Associated Acute Myocardial Injury With Prolonged Troponin Elevation
Authors: Tran Ly , Ervin Charlie , Thomas Mathew J , Moore David , Sampath Rahul , Isserman Steve
Published: May 2021

Introduction:
Acute myocardial injury in the setting of COVID-19 has been well described and is associated with higher mortality.

Hypothesis:
Myocarditis has been reported as a rare cause of myocardial injury in at least seven recent case reports.

Methods:
A 70-year-old man with coronary artery disease status post bypass surgery with recent hospitalization for left shoulder septic arthritis with MSSA bacteremia was readmitted 10 days later with a positive PCR test for SARS-CoV-2 at a local nursing facility. His symptoms were dyspnea, chest pain, fever, nausea, and diarrhea. Previous hospitalization he underwent evaluation for chest pain with cardiac catheterization revealing ejection fraction (EF) of 45% and patency of all three grafts.

Results:
Laboratory investigation showed elevated markers of myocardial injury with high sensitivity troponin I (hs-TnI) of 17,643 ng/L and B-type natriuretic peptide of 2,627 pg/mL, elevated C-Reactive Protein, D-dimer, and sedimentation rate. Chest X-ray showed hazy opacity in the infrahilar right lung. ECG notable for a first degree AV block with no ST-segment elevation. Transthoracic echocardiogram (TTE) showed an EF of 20% with global left ventricular dysfunction with hypokinesis of the right ventricle. No evidence of pericardial effusion. Blood cultures were negative. Management of heart failure led to clinical improvement. Over the next three months, Hs-TnI level stayed elevated at 11,339 ng/L for four weeks and trended down to 6,791 ng/L. The patient was seropositive for COVID-19 IgG eight weeks after the diagnosis of COVID-19 was made.

Conclusions:
We report the first case of COVID-19 related myocardial injury with prolonged and extreme troponin elevation. Recent favorable cardiac catheterization further supports immune mediated myocarditis over ischemic cardiomyopathy. Unfortunately, no endomyocardial biopsy has been performed.
Abstract 16922: Extremely Elevated Natriuretic Peptide is Associated With Incident Dialysis in Chronic Heart Failure Patients With Acute Kidney Injury
Authors: Chaikijurajai Thanat , Demirjian Sevag , Wu Yuping , Tang Wai Hong W
Published: May 2021

Introduction:
NT-proBNP has been widely used as a diagnostic and prognostic marker for both acute and chronic HF. Previous studies suggested that impaired renal function was the major contributor of an extreme elevation of NT-proBNP levels in patients with chronic HF rather than elevated cardiac filling pressure. Therefore, extremely elevated NT-proBNP levels may provide prognostic value in patients with cardiorenal syndrome.

Hypothesis:
Extremely elevated NT-proBNP levels are predictive of incident dialysis and dialysis dependence in chronic HF patients developing AKI

Methods:
Electronic medical records of 478 adult chronic HF patients admitted to the Cleveland Clinic between 2011 and 2016, who developed AKI during the hospital stay and had baseline NT-proBNP before renal consultation were reviewed. We analyzed the association between baseline NT-proBNP and incident dialysis, and dialysis dependence. Dialysis dependence was defined as patients undergoing dialysis within 72 hours of discharge.

Results:
Mean age was 67.6±13.3 years, 55.9% were male, and 37.7% had CKD. There were no significant differences in baseline characteristics and serum creatinine between patients with and without incident dialysis. Median NT-proBNP was 7,994 pg/mL (IQR; 3,109-19,357 pg/mL). There were 207 (43.3%) patients required dialysis, and 138 patients (66.7%) became dialysis dependent. Higher NT-proBNP was associated with increased risk of incident dialysis (Q 4 vs 1, OR 1.85, 95% C.I. 1.10-3.09,
P
=0.020), and dialysis dependence (Q4 vs 1, OR 2.96, 95% C.I. 1.25-7.00,
P
=0.014). However, in multivariate analysis adjusting for age, gender, hypertension, and baseline creatinine, only the association between NT-proBNP and incident dialysis remained statistically significant (Q4 vs 1, OR 1.77, 95% C.I. 1.03-3.02,
P
=0.038, Figure).

Conclusions:
Extremely elevated NT-proBNP was independently associated with incident dialysis in chronic HF patients developing AKI.
Abstract 16935: Cardiovascular Disease in Head Neck Squamous Cell Carcinoma Patients - A Case-Control Study Using Electronic Medical Records Data
Authors: Mukherjee Amrita , Wiener Howard , Griffin Russell , Nabell Lisle M , Lenneman Carrie G , Lewis Cora E , Shrestha Sadeep
Published: May 2021

Introduction:
Cancer survivors have higher rates of cardiovascular disease (CVD) compared to age-adjusted general population. However, traditional CVD risk factors alone do not fully explain increased CVD risk in cancer patients. Cancer-related factors like cancer site, stage and chemotherapy may also contribute to CVD. Despite increase in head neck squamous cell carcinoma (HNSCC) cases in recent years, little is known about CVD risk in HNSCC patients. We aim to assess association of traditional risk factors and cancer-related factors with CVD in HNSCC patients.

Methods:
Electronic medical records data of 2391 HNSCC patients diagnosed between 2012-2018 at the UAB O’Neal Comprehensive Cancer Center, were included. ICD-9/10 codes were used to identify HNSCC patients, CVD cases and traditional risk factors. CVD cases were defined as those with composite events of ischemic heart disease and/ or heart failure; controls were without any CVD diagnosis. Cancer site, stage and treatment were included. Logistic regression [OR(95%CI)] was used to assess association of risk factors with CVD, adjusting for age, race, and gender.

Results:
HNSCC patients were mostly white (82.7%), male (74.7%) and had Stage III/IV cancer (46.6%). Oral cavity was the most common cancer site (32.9%), followed by oropharynx (31.7%); 55.4% patients had hypertension, 23.0% had dyslipidemia, and 16.1% had diabetes. CVD was diagnosed in 16.1% patients, who were more likely to be older [median age 67.0 vs 60.0 years, p<0.0001]. In the multivariable model, hypertension [2.08(1.54-2.80)], diabetes [2.03(1.52-2.70)] and dyslipidemia [2.36(1.82-3.07)] were associated with CVD. Smoking status was not associated. Association of cancer stage with CVD varied by cancer site. Stage III/IV oropharynx cancer patients had lower odds of CVD than stage I/II oropharynx patients [0.38(0.30-0.92)]. No association with cancer stage was observed in oral cavity patients. Compared to chemotherapy, surgery [0.85(0.63-1.14)] and other treatments {0.61(0.41-0.89)] had lower odds of CVD.

Conclusions:
Traditional CVD risk factors remain associated with CVD in HNSCC patients. In addition, cancer-related factors (oropharynx cancer, advanced cancer stage and chemotherapy) are also associated with CVD.
Abstract 16948: A Comprehensive and High Accurate Pipeline for Mouse Retinal Vasculature Characterization
Authors: Wang Xuelin , Wang Shumin , Zhu Guofu , Rhen Jordan , Pang Jinjiang , Zhang Zhengwu
Published: May 2021

Rationale:
Vascular morphological features reflect the vessel biological functions and analysis of these features is critical for understanding physiological and pathological process of vascular development and vascular diseases. Mouse retinal vasculature is a well-recognized and commonly used animal model for angiogenesis and microvascular remodeling. Thus, a powerful tool to analyze morphological changes of retinal vasculature is in urgent need.

Objective:
Develop a comprehensive and high accurate pipeline to analyze morphological changes of mouse retinal vasculature.

Methods and Results:
Retinas from postnatal mice at P2-P7 are harvested and retinal vasculatures are visualized by isolectin B4 whole mount staining. A comprehensive software, Vessel Tech, is developed to perform vessel segmentation, network reconstruction and analysis. Vessel Tech relies on recent advancements in the convolutional neural network and techniques from network data analysis to provide high accuracy vascular identification and comprehensive vascular morphological feature extraction. Compared with existing blood vessel analysis softwares, Vessel Tech shows great improvement in accuracy. Based on the reconstructed vessel network, various metrics of angiogenesis and micro-remodeling are extracted and statistically analyzed.

Conclusions:
We generated and verified a novel pipeline, named “Vessel Tech”, which could automatically process retinal vascular images, reconstruct vessel network with high accuracy and assay global and local vascular characteristics. The development of Vessel Tech provides a powerful tool to precisely study the physiological and pathological variations during vascular development and vascular diseases.
Abstract 16954: Effect of a Multifaceted Quality Improvement Intervention on the Prescription of Cardiovascular Prevention Treatments in Patients With Coronary Artery Disease Insights From the Bridge Cardiovascular Prevention Cluster Randomized Trial
Authors: Machline Carrion M. Julia , Soares Rafael M , Penna Guimaraes Helio P , Nakagawa Renato H , Damiani Lucas P , Fonseca Francisco A , Izar Maria C , Pontes-neto Octavio M , Amodeo Celso , Barros Pedro G , Stein Airton T , Piegas Leopoldo S , Lopes Renato D , Berwanger Otavio B
Published: May 2021

Introduction:
Moving toward evidence-based care protocols is key to reduce the burden of cardiovascular diseases.

Hypothesis:
We assessed the hypothesis that a multifaceted intervention could improve the adherence to evidence-based therapies for coronary artery disease patients.

Methods:
The BRIDGE Cardiovascular Prevention study was a cluster randomized trial including 1,619 patients with ischemic stroke, coronary artery disease or peripheral artery disease from 40 outpatient clinics in Brazil. Clusters were randomized to receive a multifaceted quality improvement intervention or to routine practice. The intervention included reminders, care algorithms, training of a case manager, audit and feedback reports, and distribution of educational materials to health care providers. The primary endpoint was the adherence to combined use of statins, antiplatelets and ACEi or ARBs, using an “all or none” approach at 12 months in patients without contra-indications.

Results:
Among the 1619 patients enrolled in the original sample, 1327 (81.9%) were coronary artery disease patients. The mean age was 65.7 (SD=10.4) and 880 (66.3 %) were men. There was a significant difference in the combined prescription of evidence-based therapies between the intervention and the control groups (75.4% versus 61.8 % respectively, Odds Ratio, 2.33 [95% CI, 1.29 - 4.21], p<0.01). Patients in the intervention group were more likely to receive statins (94.4% vs. 84.7%; Odds Ratio 4.15 [95% CI, 1.62 - 10.61], p<0.01) and antiplatelet (95.3% vs. 89.0%; Odds Ratio 3.32 [95% CI, 1.45 - 7.58], p<0.01). There was no significant difference in the occurrence of major cardiovascular events (non-fatal myocardial infarction, non-fatal stroke and mortality) between groups (2.34 % vs. 3.08%; Hazard Ratio 0.76 [95%CI, 0.39-1.49, p=0.42]. For patients with myocardial infarction the combined prescription of evidence-based therapies was increased in the intervention group as compared to the control group (75.6% versus 62.3 % respectively, Odds Ratio, 2.12 [95% CI, 0.99 - 4.54], p=0.02).

Conclusions:
Among coronary artery disease patients treated in Brazil, a quality improvement intervention resulted in improved prescription of evidence-based therapies for cardiovascular prevention.
Abstract 16989: Clinical Outcomes of Atrial Fibrillation With Hyperthyroidism
Authors: KHAN MUHAMMAD ZUBAIR Z , Patel Kirtenkumar , Gupta Ashwani , Hodge Jordesha , Patel Krunalkumar , Zarak Muhammad S , Jarrar Ahmad , KOROL NATALIIA , Kutalek Steven P
Published: May 2021

Introduction:
Atrial fibrillation (Afib) is a common cardiac manifestation of hyperthyroidism. The data regarding outcomes of A fib with and without hyperthyroidism are lacking.

Hypothesis:
We hypothesized that patients with Afib and hyperthyroidism have better clinical outcomes, compared with Afib patients without hyperthyroidism.

Methods:
We queried National Inpatient Sample database for years 2015 - 2017 using Validated International Classification of Diseases and Clinical Modification (ICD-10-CM) codes for atrial fibrillation and hyperthyroidism. Patients were separated into 2 groups- A fib with hyperthyroidism and A fib without hyperthyroidism.

Results:
Study was conducted on 68,095,278 pateints. A total of 9,727,295 Afib patients were identified, out of which 90,635(0.9%) had hyperthyroidism. The prevalence of hyperthyroidism was higher in patients with Afib (0.9% vs 0.4%, p value <0.001), compared with patients without A fib. Using multivariate regression analysis after adjusting for various confounding factors, the odds ratio of Afib with hyperthyroidism was 2.08 (CI 2.07 - 2.10 P<.0001). Afib patients with hyperthyroidism were younger, (70.9 vs75.1 years, p<0.0001) and more likely to be female (63.9% vs 47% p<0.0001) as compared with Afib patients without hyperthyroidism. Afib patients with hyperthyroidism had lower prevalence of CAD (36.4% vs 43.8%,p<0.0001), cardiomyopathy(24.1% vs 25.9%,p<0.0001), valvular disease (6.9% vs 7.4%,p<0.0001), hypertension(60.7% vs 64.4%,p<0.0001) , and diabetes mellitus (28.9% vs 31.8%,p<0.0001). Afib with hyperthyroidism group had lower all-cause mortality (3.3% vs 4.8%, p<0.0001), shorter mean length of stay (5.7 ±6.6 vs 5.9±6.6 days,p<0.0001) and hospitalization cost ($14968±21871 vs $15955±22233, p<0.0001). The disposition to home was higher in Afib with hyperthyroidism patients (50.6% vs 41.8 p<0.0001).

Conclusions:
Presence of hyperthyroidism is associated with Afib in both univariate and multivariate analysis. Afib patients with hyperthyroidism have better clinical outcomes, compared with Afib patients without hyperthyroidism.
Abstract 16994: Left Ventricle Accessory Antero-Septal Papillary Muscle Detected in the LVOT Vicinity by Means of Cardiac MRI and Echocardiography in HOCM and Control Patients
Authors: Angheloiu George O , Biederman Robert W
Published: May 2021

Background:
We studied by means of echocardiography (echo) and cardiac MRI the occurrence of an accessory papillary muscle that unites mostly the left ventricle (LV) apex with the basal or mid antero-septum.

Methods:
We included all good quality studies as reviewed by two cardiologists and assessed the occurrence of a contractile papillary muscle situated between the LV apex and antero-septum.

Results:
A contractile accessory papillary muscle situated between the LV apex and the antero-septum was seen in 100% of HOCM patients and 62% of control patients (p=0.05, panels 1-6 HOCM patients and 7-9 controls; panels 1, 4 and 7 - diastole; 2,5 and 8 - early-systole; 3, 6 and 9 - end-systole) in the cardiac MRI images acquired from a total of 22 HOCM (9) and control (13) patients. The same structure was observed in 241 patients representing 69.5% of all-comers echo studies. The age was 69 ± 17 years on average in the echo arm, patients harboring the antero-septal accessory muscle being older (71.6 + 15.7 years old vs 63.5 ± 18.1 for those without, p=0.0005). We exemplify this structure by parasternal long axis still echo images from 24 patients (panel 14) as well as more detailed images from 4 patients in the same group (panels 10-13). Red arrows point out the accessory antero-septal papillary muscle and white arrows the antero-septum. Pink and yellow dots neighbor the regular antero-lateral and postero-medial pap muscles and the white dots the mitral valve.

Conclusion:
A contractile accessory papillary muscle was observed in slightly more than half of the all-comer echo studies, and in all HOCM patients in the cardiac MRI arm. Further research is needed to fully characterize the anatomical and physiological significance of this structure attaching in the immediate vicinity of the LVOT in HOCM and control patients.
Abstract 16998: Gender and Age Specific Baseline Predictors of MACE in PEACE Trial Identified by Machine Learning
Authors: Xin Victoria , Hayashi Scout , Husain Anwar , Hasan Ahmed A , Dey Amit , Banerjee Avantika , Atkinson Ian , Dandi Gauri , Qureshi Khizar , Lewis Natalie , Mahmood Nayab , Hasan Noah , Haq Nowreen , Gani Nuha , Mallick Zyannah , Rosenberg Yves D
Published: May 2021

Introduction:
The NHLBI supported Prevention of Events with Angiotensin-Converting Enzyme (ACE) Therapy trial (PEACE) (NCT00000558) found that the addition of ACE inhibitor trandolapril to conventional therapy in 8290 patients with stable coronary artery disease and preserved ejection fraction provided no benefit against MACE (cardiovascular death, nonfatal myocardial infarction, or the need for coronary revascularization), the composite primary endpoint. We reused publicly available individual patient-level PEACE data from NHLBI Data Repository (BioLINCC) to perform hypothesis-generating secondary analyses by machine learning (ML) using random survival forest (RSF) to identify gender and age group specific predictors for MACE.

Methods:
RSF was performed on 50 baseline variables for the MACE outcome in male and female and in age group (<60, 60-69, >69) cohorts. The top ten predictors identified in each cohort were included in a multivariate analysis using a Cox proportional hazards model with a multiple regression approach.

Results:
The top 10 predictors for the MACE selected by RSF are shown in Figure 1. Expected cardiovascular (CV) risk predictors like blood pressure, Canadian CV Society angina classification (CCS), age, and a history of various CV procedures consistently emerge amongst the top ten predictors of the primary MACE outcome across all gender and age specific subgroups. Interestingly, RSF also identified renal function biomarkers like serum potassium and glomerular filtration rate as common top ten predictors.

Conclusion:
Using ML, we uncovered in an unbiased fashion, gender and age groups specific unanticipated top predictors for MACE in PEACE trial. This underscores the value of gender and age specific predictors to examine the efficacy and outcomes of therapeutic interventions in advancing precision and personalized medicine.
Abstract 17006: Reversing Membrane Clock Remodeling (MCR) Associated With Heart Failure With Preserved Ejection Fraction (HFpEF) in the Sinoatrial Node (SAN) Eliminates Chronotropic Incompetence (CI)
Authors: Liang Jialiu A , Sompel Kevin , Yu Joseph K , Mesquita Thassio , Marban Eduardo , Cingolani Eugenio , Trayanova Natalia
Published: May 2021

Introduction:
While CI, or the inability of heart rate (HR) to adequately respond to exercise, is a strong indicator of mortality in HFpEF, treatment options remain limited as its mechanisms remain underexplored. Ionic remodeling of the SAN, both of the membrane (MC) and calcium clocks (CC), is associated with HFpEF and CI.

Aim:
Using an
in silico
approach, we investigated whether SAN ionic remodeling can contribute to 3 different CI presentations (Fig A) and explored the effectiveness of targeting the remodeling of the MC or CC (MCR and CCR, resp.) in eliminating CI.

Methods:
A human SAN model (control) was used, in which ionic remodeling was integrated using experimental data from HFpEF rat model with CI (Fig B top). A family of HFpEF SAN models (n = 147) was generated because the uniqueness of Ca
2+
handling parameters constrained to experimentally-based Ca
2+
transients could not be guaranteed (Fig B middle). To assess the level of CI, max beat rate (BR), BR response (τ
on
), and BR recovery (τ
off
) were quantified for each model in response to a transient 40s pulse of 1 μM isoproterenol (ISO) (Fig B bottom). Lastly, the effect of reversing either CCR or MCR on CI was determined.

Results:
Without ISO, BR of HFpEF SAN models was similar to that of control; when ISO was applied (Fig C), HFpEF models exhibited all aspects of CI: submaximal BR (Fig D), and elevated τ
on
and τ
off
(Fig E). In CCR reversed models, BR without ISO was similar to that of control; with ISO, they exhibited submaximal BR (Fig F). In MCR reversed models, BR without ISO was slightly lower compared to control; with ISO, while they exhibited submaximal BR, the increase in BR with ISO was similar to that of control (Fig F). τ
on
and τ
off
were elevated in CCR reversed models, but they were not in MCR reversed models (Fig G). In summary, CCR reversed models exhibited all aspects of CI, but MCR reversed models did not.

Conclusion:
Ionic remodeling of the SAN contributes to CI in HFpEF, and targeting MCR could be a promising strategy for eliminating CI.
Abstract 17020: Nationwide Analysis to Determine Mechanical Circulatory Support Device Use in Mechanical Complications of Acute Myocardial Infarction
Authors: shaik ayesha , Gonuguntla Karthik , Perosevic Nikola
Published: May 2021

Introduction:
Without timely reperfusion therapy, acute myocardial infarction (AMI) can lead to mechanical complications (MC) such as papillary muscle rupture (PMR), ventricular septal rupture (VSR), free wall rupture (FWR). Mechanical circulatory support (MCS) devices such as intra-aortic balloon pump (IABP), Impella and extracorporeal membrane oxygenation (ECMO) are used in cardiogenic shock associated with AMI-MC.

Hypothesis:
As per the SHOCK-II trial use of MCS in MI complicated cardiogenic shock showed no difference in mortality. We sought to determine the rates of AMI-MC, MCS device placements and outcomes associated with them.

Methods:
The Nationwide Inpatient Sample was queried from 2010 to 2014 using ICD-9 codes with a primary diagnosis of AMI. We also used diagnosis and procedure codes for MC and MCS devices. We excluded patients with NSTEMI.

Results:
From 2010 to 2014, we identified 3158 hospitalizations related to AMI-MC with a mean age of 64±13.4 years. Majority were men 69% with 75% Caucasian with an in-hospital mortality rate of 37%. Use of MCS was most common in males (67%), Caucasians (77%), and with an age group of 50-70 years (54%). Of these patients, PMR was noted in 13%, VSR in 31% and FWR in 56%. Rates of MCS devices were 38% (IABP 35%, Impella 3% and ECMO 4%). Overall use of MCS for FWR, VSR, PMR were 15%, 61%, 80%. Percentage of MC requiring IABP, Impella, ECMO were as follows; FWR (15%, 0.6%, 0.3%), VSR (58%, 7%, 6%), PMR (70%, 5%, 12%). Patients that received cardiac transplant was 0.2%. In-hospital mortality among patients who received MCS to those who did not receive MCS were 59% vs 24%; p<0.001, among patients who received IABP to those who did not receive any MCS were 54% vs 24%; p<0.001 and among patients who received Impella to no MCS were 86% vs 24%; p<0.001.

Conclusions:
Based on the results, FWR was the most common MC. MCS were most commonly used in PMR followed by VSR, with IABP being the most common type. Patients on MCS had increased in-hospital mortality compared to those without MCS. Large randomized trials are needed to determine the effectiveness of these devices in predicting outcomes associated with AMI-MC
Abstract 17024: Clinical and Echocardiographic Predictors of Death and Hospital Readmission in Patients With Recent Onset Severe Secondary Tricuspid Regurgitation
Authors: Nichols Katherine M , Milbridge Andrew , Andrus Bruce W
Published: May 2021

Introduction:
Tricuspid regurgitation (TR) is often asymptomatic leading to delayed diagnosis. Predictors of decompensation and indications and timing for intervention are not well delineated. We studied the clinical and echocardiographic outcomes of patients with recent onset severe, secondary TR to identify risk factors for death, hospital readmission and hepatobiliary disease.

Methods:
We queried our institutional echo database to identify all patients with severe secondary TR in 2010 and a TTE within the previous two years prior showing less than moderate disease. Baseline and follow up clinical and echocardiographic variables over the subsequent 10 years were collected retrospectively. We analyzed our data for predictors of death, hospital readmission, and hepatobiliary disease.

Results:
We identified 34 patients. Over 10 years of follow up, 27/34 (79%) of the patients died. Elevated pulmonary artery systolic pressure (PASP) was a significant predictor of death. PASP was 48 mm Hg in those who died compared to 33 mm Hg in those who survived (p=0.02) (Figure 1). Pulmonary hypertension (PH) and pulmonary embolism (PE) were predictors of readmission. A history of PH was present in 7/10 (70%) of patients requiring readmission compared to 7/24 (29%) in those who did not require readmission (p=0.03). A history of PE was present in 2/10 (20%) of those requiring readmission compared to 0/24 (0%) of those who did not require readmission (p=0.02). No patients were diagnosed with hepatobiliary disease.

Conclusions:
New onset severe, secondary TR is associated with a high ten year mortality rate. Elevated PASP is a predictor of death and history of PE and pulmonary HTN are predictors for hospital readmission.
Abstract 17028: Single Cell Analysis of T Cells Found in Atherosclerotic Plaque
Authors: NGUYEN Patricia K , Chowdhury Roshni R , D'Addabbo Jessica , Sasagawa Koki , Huang Xianxi , Louis David M , Gulati Gunsagar S , Koyano Tiffany K , Fong Robyn , Li Jinliang , Maecker Holden T , Boyd Jack , Chen Yueh-Hsiu , Chan Charles , Davis Mark
Published: May 2021

Background:
Despite advances in medical therapy, heart attack and stroke remain leading causes of morbidity and mortality. Biological, epidemiological, and clinical studies have shown that many patients (up to 33% in some trials) still have residual inflammatory risk that is associated with plaque rupture, even in the setting of low LDL.

Methods and Results:
In this study, we analyzed the T cell landscape of coronary atherosclerotic plaque to determine their role in the development of atherosclerosis and its adverse sequelae. We recruited 17 patients undergoing heart transplantation. From each explanted heart, we obtained plaques from the major coronary arteries, digested them to form a single cell suspension, sorted the arteries for CD4 and CD8 T cells into 96 well plates, and submitted them for single cell genotyping and phenotyping (
Figure 1
). Although peripheral blood from these patients also contains T cell clones, plaque CD8 T cell clones appear to function differently than blood (e.g., producing more BCL6, TNF-, and interferon gamma) further supporting that this is not a bystander effect. We found CD4 and CD8 T cells with identical TCR sequence across the arteries of the same patient, suggesting CD8T cells are purposely recruited to the plaques. When we analyzed the percent clonality based upon location and disease severity, we find that clonality is not dependent on location and is present at all severity levels, especially, in early disease (e.g., AHA Type I-IV lesions.

Conclusion:
CD8 T cells are clonally expanded in atherosclerotic plaque and appear to function differently than blood, suggesting these cells are purposefully recruited.
Abstract 17031: Noninvasive CT-Based Hemodynamic Assessment Using 3D Printing and Virtual Functional Assessment Index
Authors: Kolli Kranthi K , Zahid Abdul , Caprio Alexandre , Xu Patricia , Shepherd Robert , Jang Sun-joo , Doshi Tejas , Zgaren Mohamed , Kashyap Varun , Jalal Sahar , Torabinia Matin , Shaw Leslee J , Lin Fay Y , Mosadegh Bobak , Dunham Simon
Published: May 2021

Background:
Virtual functional assessment index (vFAI), an alternative approach for assessing hemodynamic significance of stenosis has been shown to enhance the diagnostic performance of coronary computed tomography angiography (CCTA) based on evaluating the area under pressure drop-flow curve for a stenosis. Previously, this was assessed via computational fluid dynamics. We investigated the evaluation of vFAI from CCTA images using 3D printing and an
in vitro
flow loop and its efficacy as compared to the invasively measured fractional flow reserve (FFR).

Methods and Results:
Eighteen patients with varying degrees of coronary artery disease who underwent non-invasive CCTA scans and invasive FFR of their left anterior descending coronary artery (LAD) were included. The LAD artery was segmented and reconstructed using Mimics (Materialise inc.,). The segmented models were then 3D printed using Carbon 3D printer (Carbon Inc.,) with rigid resins. An in vitro flow circulation system representative of invasive measurements in a cardiac catheterization laboratory was developed to experimentally evaluate the hemodynamic parameters of pressure and flow (Fig A). For each model, a range of physiological flow rates was applied by a peristaltic steady flow pump and titrated by a flow sensor. The pressure drop and the pressure ratio (Pd/Pa) were assessed for patient-specific aortic pressure and differing flow rates. vFAI was evaluated as the normalized area under the P
d
/P
a
vs Q curve from 0 to 240 mL/min. There was a strong correlation between vFAI and FFR, (R = 0.83, p < 0.001; Fig B) and a very good agreement between the two parameters by Bland-Altman analysis. The mean difference of measurements from the two methods was 0.06 (SD = 0.08, p=0.0063; Fig C), indicating a small systematic overestimation of the FFR by vFAI.

Conclusions:
vFAI can be effectively derived from 3D CTCA datasets using 3D-printed
in vitro
models, based on evaluation over a range of hemodynamic conditions.
Abstract 17055: Novel Dual mTOR Inhibitor/AMPK Activator Mitigates Doxorubicin Cardiotoxicity and Potentiates Its Chemotherapeutic Efficacy Against Triple Negative Breast Cancer
Authors: Das Anindita , Hovsepian Sahak , Das Sayantanee , Samidurai Arun , Mauro Adolfo G , Cain Chad , Kraskauskas Donatas , Corral Laura , Fung Leah , Sullivan Robert , Chan Kyle W , Swindlehurst Cathy A , Salloum Fadi N
Published: May 2021

Background:
Doxorubicin (DOX) is a first-line anticancer drug for the treatment of triple negative breast cancer (TNBC). However, its dose-dependent delayed and progressive cardiotoxicity limits its therapeutic application. NovoMedix (NM922) is a novel dual mTOR inhibitor/AMPK activator that was shown to attenuate adverse cardiac remodeling and fibrosis in a pressure-overload mouse model of heart failure. We investigated whether combination therapy with DOX and NM922 exhibits synergistic chemotherapeutic effect while mitigating DOX cardiotoxicity.

Methods & Results:
Tumors were generated in athymic female BALB/cAnNCr-nu/nu mice by implanting MDA-MB-231 cells into the rear right flank. Mice with tumors (volume≈200mm
3
) were randomized into 6 groups and treated as follows: 1) Control (n=10); 2) DOX (3 mg/kg; i.p. twice weekly, total 15 mg/kg; n=10); 3) NM922 (25 mg/kg/d; p.o. n=5); 4) DOX+NM922 (25 mg/kg/d; p.o. n=15); 5) NM922 (100 mg/kg/d; p.o. n=5); 6) DOX+NM922 (100 mg/kg/d; p.o. n=15). Tumor size, body weight and cardiac function were assessed throughout the study. DOX alone, and to a significant extent when in combination with NM922 (25 mg/kg) reduced tumor growth compared to control. NM922 (100 mg/kg) with/without DOX significantly reduced tumor growth as compared to DOX alone (Fig A). DOX caused reduction in body weight and survival of tumor-bearing mice. NM922 did not prevent DOX-induced cachexia, but significantly improved survival in DOX-treated mice (Fig B). DOX treatment caused a significant decline in left ventricular ejection fraction compared to control over 3 weeks, which was ameliorated with NM922 (100 mg/kg) co-treatment (Fig C&D).

Conclusion:
Our results suggest that NM922 may potentiate the chemotherapeutic efficacy of DOX in TNBC, while mitigating its cardiotoxicity. Moreover, these findings advocate the potential efficacy of utilizing lower DOX dosages when combined with NM922, which would have significant clinical implications.
Abstract 17061: Impact of Maternal Anxiety on
In Vivo
Placental Development in Fetuses With Congenital Heart Disease
Authors: Lu Yuanchiao , Kapse Kushal , Andersen Nicole , Andescavage Nickie , Fry Andrea , Lopez Catherine , Krishnan Anita , Bulas Dorothy , Donofrio Mary , Limperopoulos Catherine
Published: May 2021

Introduction:
Studies have shown that maternal stress and anxiety during pregnancy have been associated with a higher incidence of preterm birth and low birth weight. However, the relationship between prenatal maternal mental distress and placental development in fetuses with congenital heart disease (CHD) is unknown.

Hypothesis:
We tested the hypothesis that elevated maternal anxiety is associated with altered placental morphology in fetuses with CHD.

Methods:
A total of 141 pregnant women were recruited prospectively (control: 91; two-ventricle/2V CHD: 29; single-ventricle/SV CHD: 21), in which 228 fetal MR scans were performed (gestational age: 31.8±4.5 weeks). Single shot fast spin echo T2-weighted images were acquired on a 1.5 Tesla GE MRI scanner. Placenta tissue was manually segmented, and slice-to-volume registration was used for motion correction and 3D reconstruction. Six placental features were calculated: volume, thickness, elongation, surface area, mean diameter, and umbilical cord centricity. We completed the Spielberger State (SSAI) and Trait (SSAI) Anxiety Inventory at each study visit. Linear mixed models were utilized to analyze the placental features predicted by maternal anxiety.

Results:
Placental volume, surface area, and mean diameter were decreased with elevated SSAI in 2V CHD fetuses, while volume and cord centricity were increased with higher SSAI in SV CHD fetuses. Lower cord centricity was associated with elevated STAI in 2V CHD fetuses, and elongation was positively associated with STAI in SV CHD fetuses. There were no associations between anxiety measures and placental features in control fetuses.

Conclusions:
We report for the first time that elevated prenatal maternal anxiety is associated with altered
in vivo
placental structures in pregnancies complicated by fetal CHD. Our data suggest that disturbances in placental structure vary based on the type of fetal CHD (SV vs. 2V) in the setting of elevated prenatal maternal anxiety.
Abstract 17072: Acetylcholine Signaling and Endothelial to Mesenchymal Transition in Pulmonary Arterial Hypertension
Authors: Fernandez Nicolas Ana , Vang Alexander , Mancini Thomas , da Silva Goncalves Bos Denielli , Clements Richard T , Zhang Peng , Choudhary Gaurav
Published: May 2021

Introduction:
Pulmonary arterial hypertension (PAH) is characterized by severe pulmonary vascular remodeling. Transition of endothelial cells (EC) to mesenchymal cells (EndMT) contributes to vascular remodeling; however, the role of EndMT and underlying mechanisms in PAH remain unclear. While nicotinic acetylcholine (Ach) receptor (nAChR)-mediated pathway regulates epithelial to mesenchymal transition and promotes mesenchymal cell proliferation, its role in EndMT is unknown. In this study, we investigate EndMT in PAH and delineate the mechanisms.

Methods:
PAH was induced in Sprague Dawley rats by SU5416 (20 mg/kg; s.c.), followed by 3 wks of hypoxia (3 wk PAH) or 3wks of hypoxia with additional 4 wks of normoxia (7 wk PAH). Rats without SU5416 and kept at normoxia served as controls. At the end of experiments, hemodynamic measurements were performed. Lung EC were then isolated and purified using CD31 antibody conjugated beads and passage 3-4 were used. EndMT was assessed by dual staining of EC markers (von Willebrand factor and Griffonia simplicifolia) and α-smooth muscle actin (α-SMA) and by the mRNA expression of EC and mesenchymal genes. Lung ACh was measured by ELISA.

Results:
PAH rats had elevated PA pressures at both 3 wk (PAH vs. CON in mm Hg: 77.3 vs. 24.8, p<0.05, n=4-5) and 7 wk (65.5 vs. 28.6, p<0.05, n=10-12). EndMT was evidenced in PAH (% of cells positive with both EC markers and α- SMA: 3 wks: PAH 4.2% vs. CON 1.6%, p<0.05; 7 wks: PAH 38.5% vs. CON 4.5%, p<0.05), which was associated with significantly increased expression of mesenchymal gene (CD44, PAI1, and α-SMA) and decreased expression of vascular endothelial cadherin at 7 wk. The lungs of PAH rats had higher levels of ACh (PAH vs. CON in pg/mL, 3wk: 78.7 vs. 47.3, p<0.05, n=7; 7wk: 85.1 vs. 45.6, p<0.05, n=7). A significant increase in α7 nAChR expression was found in 7wk PAH EC.
In vitro
, treatment with ACh markedly induced EndMT in lung EC from normal rats, which was assessed by increased dual staining of EC markers and α-SMA and increased expression of mesenchymal genes (α-SMA, PAI1, and pro-collagen 1, p<0.05 for all).

Conclusions:
EndMT in PAH is associated with increased lung ACh levels and α7nAChR expression in lung ECs. ACh/nAChR-mediated EndMT may contribute to the vascular remodeling in PAH.
Abstract 17074: Methadone Potently Blocks Cardiac IK1 Leading to Membrane Instability
Authors: Klein Michael , Geiger Robert , Krantz Mori J , Goldstein Robert , Flagg Thomas P , HAIGNEY Mark C
Published: May 2021

Introduction:
Methadone is the second most frequently reported cause of drug-induced cardiac arrest in pharmacovigilance databases, yet the mechanism of its pro-arrhythmia is unclear. Methadone-induced QTU wave prolongation has been repeatedly observed and attributed to inhibition of the delayed rectifier hERG current, but QTU fusion suggests the inwardly rectifying K
+
current (IK1) might also be affected by methadone.

Hypothesis:
Methadone pro-arrhythmia is associated with potent block of the IK1 current responsible for rapid terminal repolarization of the cardiac action potential (AP).

Methods:
Human Kir2.2, encoding the IK1 current, was transiently expressed in COS cells. hERG1a was stably expressed in CHO cells. Cardiac myocytes from swine were obtained by ventricular enzymatic dissociation. Ionic current and APs were measured using patch-clamp methods. Methadone HCl (R+S racemates) was dissolved in Tyrode solution.

Results:
Methadone suppressed IK1 current with an IC
50
of 1.47 uM (Fig 1A). Methadone also suppressed outward IK1 (-60 mV) measured in swine myocytes (Ba
2+
-sensitive current) with an IC
50
of 1.52 μM. Methadone suppressed hERG currents with an IC
50
of 2.1 μM. APs measured in swine myocytes exhibited significant prolongation (13 ± 4 % increase of APD
90
, p<0.029, n=7) as well as slowing of the rate of terminal repolarization (a specific marker of IK1 blockade) in the presence of 1 μM methadone (Fig. 1B). Fluctuations of diastolic voltage increased by 30 ± 12 and 151 ± 27 % (n=3; p<0.04) in 0.1 and 1 μM methadone, respectively, consistent with a reduction in membrane stability.

Conclusions:
Methadone is an equipotent blocker of IK1 and hERG. The effect of IK1 block coupled with modest hERG block has a synergistic effect on terminal repolarization that may partially explain the pro-arrhythmic impact of methadone. Moreover, this observation may be generalized to other drugs where unsuspected IK1 blockade may contribute to pro-arrhythmia and torsade de pointes.
Abstract 17083: SARS-CoV-2 Dramatically Decreases Healthcare Access for Patients With Cardiovascular Disease
Authors: Harrington Josephine L , Jollis James G , Patel Manesh R , Joiner Anjni , Granger Christopher B
Published: May 2021

Background:
In the setting of SARS-CoV-2 the public has sought to avoid any unnecessary contact, leaving their homes only when absolutely necessary.

Hypothesis:
We hypothesized that patients largely stopped seeking care for their acute CV conditions as they sheltered in place in the setting of Covid-19.

Methods:
We assessed changes in access to CV medical care at multiple levels, including Emergency Medical Services (EMS) call volumes in local Durham and Orange County (population 469,000), as well as for CV clinic appointments, inpatient CV census, ST elevation myocardial infarction (STEMI) activations and Emergency Room (ER) visits for a CV complaint at Duke University Hospital, which provides care for a catchment area of about 3.9 million residents, between the first and second half of March 2020.

Results:
Interactions for CV conditions dropped significantly at almost every level of entry into the healthcare system between the first and second half of March 2020 (Table, Figure).

Conclusions:
During the current pandemic, CV patients appear to have a significantly higher threshold to seek medical care. The older population of patients with CV disease may be particularly predisposed to remain in isolation due to the higher risk. Patients not receiving medical care may be continuing to decompensate. They may be more likely to die at home, or when they do present for care it may be at a later stage, leading to increased morbidity and mortality. Understanding and addressing the profound change in acute CV care may be almost as important as controlling the virus and its direct consequences, especially as the healthcare systems begin to evaluate how to best re-engage with their patients.