bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14886: Outcome of Early Surgery in Active Infective Endocarditis in Terms of Intraoperative Valve Culture
Authors: Suzuki Kota , Yoshioka Daisuke , Toda Koichi , Miyagawa Shigeru , Kainuma Satoshi , Kawamura Takuji , Kawamura Ai , Kashiyama Noriyuki , Ueno Takayoshi , Kuratani Toru , Sawa Yoshiki
Published: May 2021

Introduction:
In recent years, the benefit of early surgery in active infective endocarditis (IE) has been reported. The drawback of early surgery is the risk that residual bacteria in the operative field may cause IE recurrence. Little is known regarding the relationship between intraoperative valve culture and recurrence. In the present study, we investigated the value of early surgery for IE based on the results of valve cultures.

Hypothesis:
Positive intraoperative valve cultures in early surgery are associated with recurrence.

Methods:
Between 2009 and 2017, 585 patients underwent valve surgery for definitive left-sided active IE at 14 affiliated hospitals. Early surgery was defined as surgery within 14 days from diagnosis, and patients with unknown valve culture results were excluded. We analyzed the short and mid-term outcome in patients with early surgery (n=228). These 228 patients were compared in two groups: positive (Group P, n=106) and negative (Group N, n=122) valve cultures. The primary outcome was all-cause mortality. Secondary outcomes were recurrence of IE. Mean follow-up time was 2.5±2.8 years.

Results:
Patients in group P had a significantly higher inflammatory response on preoperative blood tests (White blood cell count: 10.4 (8.3-14.5) vs. 8.2 (6.0-12.7) х10
3
/μl, p=0.005, C-reactive protein: 7.3 (3.8-11.0) vs. 3.8 (2.1-6.8) mg/dl, p<0.001). Patients in group P also had a significantly shorter duration from diagnosis to surgery (2 (1-4) vs. 4 (1-9) days, p<0.001). There was no significant difference in in-hospital mortality between the two groups (13/106 (12%) vs. 11/122 (9%), p=0.43). The overall survival rate at 1 and 5 years was 83% and 69% in group P, 82% and 75% in group N, respectively (p=0.85). The rate of freedom from the recurrence of endocarditis at 1 and 5 years postoperatively was 97% and 82% in group P, and 98% and 92% in group N, respectively (p=0.02). In Cox's hazard analysis, positive valve culture was a risk factor for IE recurrence in multivariate analysis (hazard ratio, 3.39; 95% confidence interval, 1.07 to 10.67; p=0.037).

Conclusions:
Positive valve culture cases in early surgery for active IE have a significantly increased risk of recurrence compared with valve culture-negative cases and require careful management.
Abstract 15117: The Catheter Uncertainty Principle: Does the Presence of a Catheter Alter Hemodynamics?
Authors: Kaplan Michael , Vardhan Madhurima , RANDLES Amanda
Published: May 2021

Introduction:
Catheters are an essential component of measuring invasive hemodynamic quantities. However, by the very nature of a catheter's presence, it acts to disturb the normal flow field, potentially altering measured pressures and derived quantities, such as FFR. Computational fluid dynamic simulations are performed to explore how vessel lumenal area and catheter size effect pressures.

Methods:
Patient-specific anatomical reconstructions are coupled with HARVEY, a massively parallel lattice-Boltzmann fluid solver, to calculate 3D blood flow around simulated catheters. We explore the effects of catheter size in vessels ranging from 5 mm in diameter, a right ventricle to pulmonary artery shunt (RVPAS) in a patient with HLHS, and smaller, in coronary arteries. Pressures sampled at the location corresponding to the distal end of the catheter are compared and FFR is calculated for the coronary models.

Results:
Figure 1A illustrates the calculated pressure waveforms for simulated catheter sizes in a RVPAS. In this case, the catheter does not significantly alter the pressure field unless unrealistically large catheters, such as a 13 Fr, are used. For adult coronary arteries (Figure 1B), reasonable catheter sizes result in appreciable decreases in sampled pressures and, consequently, in calculated FFR (Figure 1C).

Conclusion:
The presence of a sufficiently large catheter (>50% of the vessel lumenal area) causes a noticeable decrease in the pressures at the tip of the catheter. While unlikely to occur in larger vessels, this can occur during left heart catheterizations of diseased coronary arteries. This causes an artificial decrease in FFR, which can potentially alter clinical decision making. While catheters are the gold standard for pressure measurements, an improved understanding of the inherent sensitivity of their measurements to unobstructed vessel lumenal area is important for interpreting the results of catheter-based diagnostic procedures.
Abstract 15121: Mortality in Cancer Patients Undergoing Percutaneous Coronary Intervention: Insights From a Hospital-based Cross-sectional Study
Authors: Gaddam Anusha R , Ajibawo Temitope , PATEL RIKINKUMAR
Published: May 2021

Introduction:
Comorbid risk factors between cancer and coronary artery diseases (CAD) and underlying pathogenesis of inflammation and oxidative stress led to an increase in the number of cancer patients developing CAD.

Hypothesis:
The prime purpose of our hospital-based study is to evaluate the risk of mortality due to cancer and chronic comorbidities in post-percutaneous coronary intervention (PCI) patients.

Methods:
We conducted a cross-sectional study using the nationwide inpatient sample (NIS, 2012 to 2014) including 1,131,415 adult patients undergoing PCI with placement of non-drug and/or drug-eluting coronary artery stents. The logistic regression model was used to assess the odds ratio (OR) of the association between comorbid cancer and mortality in post-PCI hospitalized patients.

Results:
Most of the post-PCI patients with cancer were older adults (mean age 70.6 years), males (71.8%), and Caucasians (80.6%). Females (OR 1.28, 95% CI 1.24-1.34) had higher odds of post-PCI mortality risk compared to males. Among all comorbidities, coagulopathy and deficiency anemia were associated with increased risk of mortality by three times (95% CI 2.837-3.250) and 1.6 times (95% CI 1.534-1.692), respectively in post-PCI hospitalized patients. Comorbid cancer was associated with an increased risk of mortality in post-PCI hospitalized patients (OR 1.88, 95% CI 1.69-2.09) after controlling for potential confounders.

Conclusions:
Cancer is a significant risk factor increasing the risk of mortality by 88% in post-PCI hospitalized patients. An integrated care model requiring more vigilance and aggressive management for the complex patient population with cancer and other comorbidities are needed.
Abstract 15132: Inpatient Outcome of Infective Pericarditis in the United States: An Analysis From National Inpatient Sample 2016-2017
Authors: Liu Bolun , Chen Bing , Behnamfar Omid , Gomez Trisha , Kattoor Ajoe
Published: May 2021

Introduction:
Infective pericarditis is a relatively uncommon condition in the modern antibiotic era, has a high mortality rate (20-30%) and is associated with immunosuppression, alcohol use, illicit drug use, thoracic surgery. Outcomes data in the current era is unknown. We aim to analyze the baseline characteristics and outcomes of patients admitted in the hospital with infective pericarditis.

Methods:
We conducted a retrospective study using National Inpatient Sample (NIS) database from 2016 to 2017. Hospital visits with a primary diagnosis of infective pericarditis (ICD10, I30.1) during which a pericardial procedure was performed were identified using ICD-10-CM and ICD-10-PCS Codes. Our primary outcome was basic characteristics and in-hospital all-cause mortality. Multivariate regression model was used to adjust for the pericardial procedure approach, age, and cardiac tamponade. R (Version 3.6.1) was utilized for the analysis.

Results:
A total of 1010 weighted hospitalizations in adult patients with infective pericarditis were identified. The mean age was 56.7±1.1 years (woman - 41.4%). The baseline characteristics and comorbidities are described in table 1 and table 2. 60.5% of the patients underwent percutaneous pericardial drainage, 36.4% had open surgery, and 3.2% had VATs. The mean time from admission to a pericardial procedure is 1.7±0.2 days. In-hospital all-cause mortality was 2.27%. The mean length of stay was 7.59±0.43 days. The mean total cost was 22530±1193 US dollars. Among all hospitalizations, 61.8% of them were complicated by hemodynamic instability and 56.8% had cardiac tamponade. Compared to pericardiocentesis, patients who underwent pericardiotomy had a higher mortality (5% vs 0.8%, adjusted OR 8.03, P = 0.043).

Conclusions:
Our study demonstrates relatively low inpatient mortality with infective pericarditis compared to older studies. Around half of the patients had cardiac tamponade.
Abstract 15146: Reverse Right Heart Chambers Remodeling and Decrease in Tricuspid Regurgitation Severity After Restoration of Sinus Rhythm in Patients With Atrial Fibrillation: A Mid-term 3d Echocardiographic Study
Authors: Benhamou Tarallo Iris , SOULAT-DUFOUR Laurie , Lang Sylvie , Ederhy Stephane , Adavane-Scheuble Saroumadi , Chauvet-Droit Marion , Nhan Pascal , Jean Marie-Liesse , Ben Said Rim , Issaurat Pauline , Boccara Franck , Cohen Ariel A
Published: May 2021

Introduction:
The natural history of tricuspid regurgitation (TR) and right heart chambers remodeling in patients with atrial fibrillation (AF) according to the cardiac rhythm at mid-term follow-up has been poorly assessed.

Hypothesis:
Restoration of sinus rhythm in AF patients is beneficial to the remodeling of right heart chambers and decrease in TR severity.

Methods:
We prospectively and serially evaluated 24 consecutive patients hospitalized for AF using three dimensional (3D) transthoracic echocardiography (TTE) at admission (M0) and every 6 months during a 2 years-follow-up (FU, M6, M12, M18, M24) (120 TTE exams). Patients were divided into two groups according to their cardiac rhythm at M24: restoration to SR (SR group, n=14) and persistence of AF (AF group, n=10). TR grade severity was divided into 4 grades using an integrated approach (0: none or trace; 1: mild; 2: moderate; 3: severe TR). 3D indexed volumes (3D Vi) of the right atrium (RA) and right ventricle (RV) as well as 3D tricuspid annulus (TA) area were analyzed in end systole (ES) and end diastole (ED).

Results:
Beyond 6 months of FU, the SR group had overall significantly lower 3D ES RA Vi, 3D ED RA Vi, 3D TA ES area and TR severity in comparison with AF group (Figure). There were no significant differences between the 2 groups with regard to 3D RV Volumes and 3D ED TA area.

Conclusions:
According to our results on both TR evolution and right heart cavities reverse remodeling, strategies aiming at SR restoration in patients with AF and TR should be broadly discussed.
Abstract 15161: Increased Right Atrial Stiffness in Patients With Heart Failure With Preserved Ejection Fraction and Pulmonary Hypertension
Authors: van Wezenbeek Jessie , van der Bovenkamp Arno , Wessels Jeroen N , Mouratoglou Sophia-Anastasia , Goumans Marie Jose , vonk noordegraaf anton , Bogaard Harm J , Handoko M L , De Man Frances S
Published: May 2021

Background:
Patients with Heart Failure with preserved Ejection Fraction (HFpEF) and Pulmonary Hypertension (PH) have increased right atrial (RA) pressures. Whether the higher RA pressures are related to increased afterload or overall stiffening of the heart is unknown. The aim of this study is to gain further insight into the right atrium in HFpEF-PH.

Methods:
This is a retrospective analysis of patients with HFpEF (no PH), HFpEF-PH and Pulmonary Arterial Hypertension (PAH) that underwent right heart catheterization and cardiac magnetic resonance (CMR) imaging. CMR was used to determine RA function by quantifying volume and strain on the 4-chamber view. Total, passive and active RA emptying fraction (RAEF) were calculated. RA stiffness was calculated by determining the slope of maximum and minimum pressure during v-wave and minimal and maximal RA volumes. Groups were compared with ANOVA and post-hoc comparison with Bonferroni correction.

Results:
176 patients were included: 13 HFpEF, 33 HFpEF-PH and 130 PAH patients. Although afterload was lower in PAH and higher in HFpEF patients, as shown by mean pulmonary arterial pressure (mPAP) (41

±

2 mmHg in HFpEF-PH vs 53

±

21 mmHg in PAH vs 19

±

1 mmHg in HFpEF, p<0.001) and pulmonary vascular resistance (PVR) (2.3

±

0.3 wu/m
2
in HFpEF-PH vs 5.7

±

0.2 wu/m
2
in PAH vs 0.4

±

0.06 wu/m
2
in HFpEF, p<0.001), mean RA pressure was significantly higher in HFpEF-PH patients compared to both groups (Figure 1A). HFpEF-PH patients had significantly increased RA stiffness compared to HFpEF and PAH patients (Figure 1B). Total RAEF was reduced in HFpEF-PH compared to PAH and HFpEF patients: passive RAEF was similar, but active RAEF was slightly reduced in HFpEF-PH (Figure 1C). This was in line with measurements of RA longitudinal strain (Figure 1D).

Conclusions:
Despite lower afterload, HFpEF-PH patients have worse RA function and increased RA stiffness compared to PAH. Higher RA pressures in HFpEF-PH may reflect additional stiffening of the heart.
Abstract 15166: Automated Analysis of 12-lead Electrocardiogram for Pediatric Cardiac Disease Mass Screening in School-age Children by the Combined Use of Signal Processing and Deep Learning
Authors: Toba Shuhei , Mitani Yoshihide , Sugitani Yusuke , Ohashi Hiroyuki , Sawada Hirofumi , Yodoya Noriko , Ohya Kazunobu , Tsuboya Naoki , Umezu Kentaro , Shomura Yu , Ito Hisato , Futsuki Ayano , Ishikawa Renta , Yamasaki Takato , Takao Motoshi , Hirayama Masahiro
Published: May 2021

Introduction:
Electrocardiogram (ECG) is useful for screening children at risk of sudden cardiac death. However, high resources for manual interpretation were a drawback when undertaking mass screening; the accuracy of conventional automated ECG analysis was unsatisfactory for this purpose.

Hypothesis:
A model consisting of signal processing and deep learning is newly developed and validated to analyze ECG in school-age children and has higher accuracy than a conventional automated model.

Methods:
We obtained 12-lead ECGs performed in consecutive patients at 6-18 years of age at the inpatient or outpatient clinic of a tertiary hospital in Japan during 2003-06. Patients were randomly assigned to training (83%) and test (17%) groups. Each ECG was labeled as normal or abnormal by 3 board-certified pediatric cardiologists in accordance with the JCS guideline 2016 for school ECG screening. A model to analyze several-second digital wave data of 12-lead ECG was developed by combining signal analysis and deep learning (fast Fourier transform and deep convolutional neural network) to predict abnormality. The trained model was evaluated in the test data using ROC curve and by comparing its accuracy with that of a conventional model (Minnesota code assigned by ECG-1400, Nihon kohden, Japan).

Results:
We included 1842 ECGs performed in 1062 patients (median age 11 years, IQR, 8-14; male 56%), in which 519 ECGs (28%) were labeled abnormal. Findings include ST-T abnormality (16%), right bundle branch block (7.8%), QRS axis abnormality (5.9%), right ventricular hypertrophy (3.6%) and left ventricular hypertrophy (3.3%). Of 310 ECGs for test (27% labeled as abnormal), 20% were considered abnormal by our model, while 73% by the conventional model. Our model showed AUC of .87 and higher accuracy than the conventional model (.85 vs .47;
P
<.001, McNemar test). Sensitivity and specificity were .60 and .95 in our model; .86 and .33 in conventional model, respectively.

Conclusions:
A model combining signal processing and deep learning is newly developed and validated for analyzing 12-lead ECG in school-age children, achieving higher accuracy than a conventional model. This proof-of-concept study warrants further studies toward deep learning-based school ECG mass screening.
Abstract 15178: Mitochondrial Dynamic Modulators Mitigates Mitochondrial Dynamic Index, Biogenesis and Metabolic Impairments in Prediabetic Rats With Cardiac Ischemia-reperfusion Injury
Authors: Maneechote Chayodom , Palee Siripong , Chattipakorn Siriporn , CHATTIPAKORN Nipon
Published: May 2021

Introduction:
Long-term exposure to high-fat diet (HFD) caused obesity, which not only was positively associated with cardiovascular disorders but also had a negative impact on the outcome of acute myocardial ischemia-reperfusion (I/R) injury. Uncontrolled fission and diminished fusion of cardiac mitochondria augment the impairment of mitochondrial biogenesis and metabolism which have been implicated in metabolic diseases and I/R injury pathology. Since cardioprotective efficacy of acute administration of mitochondrial fission inhibitor (Mdivi-1) and fusion promoter (M1) have previously been reported, the effects of chronic treatment with both modulators on cardiac mitochondrial dynamics, biogenesis and lipid metabolism in prediabetic rats subjected to cardiac I/R injury have never been elucidated.

Hypothesis:
Chronic treatment of Mdivi-1 and M1 after acute myocardial I/R improve mitochondrial dynamic index, biogenesis and metabolic pathway in prediabetic rats.

Methods:
Male Wistar rats (n=18) were fed with HFD. After 12 weeks, all rats were randomly divided into: 1) HFV (Vehicle, 0.1% DMSO), 2) HFMd (Mdivi-1, 1.2 mg/kg), and 3) HFM1 (M1, 2 mg/kg) with intraperitoneal injection for 14 days. Then, all rats underwent 30 minutes of left anterior descending coronary artery occlusion followed by reperfusion for 120 minutes. The expression of mitochondrial dynamics (p-Drp1
ser616
per Mfn2 ratio or dynamic index), biogenesis (PGC1- α) and lipid metabolism (CPT1) proteins from ischemic area of heart were determined.

Results:
Chronic treatment of Mdivi-1 and M1 similarly improved cardiac mitochondrial dynamic index (p-Drp1
ser616
per Mfn2 ratio), increased PGC1-α and CPT1 expression levels, when compared to HFV (Fig).

Conclusions:
Modulating mitochondrial dynamics by chronic treatment of Mdivi-1 and M1 improved cardiac mitochondrial dynamic index, biogenesis and metabolic pathway in prediabetic rats following acute myocardial I/R injury.
Abstract 15220: Development of a Prediction Model for Atrial Fibrillation in Patients With Heart Failure and Preserved Ejection Fraction: Secondary Analysis of Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (topcat) Trial
Authors: Elkholey Khaled , Asad Zain Ul Abideen , Papadimitriou Lampros , THADANI Udho , Stavrakis Stavros
Published: May 2021

Background:
Atrial fibrillation (AF) is a common comorbidity in heart failure with preserved ejection fraction (HFpEF) and portends an increased risk of cardiovascular events. We sought to identify predictors and develop a risk score of incident AF among patients with HFpEF.

Methods:
This was an exploratory, post-hoc analysis of the TOPCAT trial. Patients without known AF were included. Cox regression was used to identify independent predictors of incident AF. A risk score was derived from the weighed sum of the regression coefficients of each independent risk factor in the final model using Cox regression analysis.

Results:
A total of 2174 patients (mean age 67.0±9.4 years; female 55%) without known AF at baseline were included. During a median follow-up of 3 years, 102 (4.7%) patients developed new onset AF. Diabetes (HR=2.1, 95% CI 1.4-3.1; p=0.0002), peripheral arterial disease (HR=2.0, 95% CI 1.2-3.4; p=0.006), elevated (>144meq/dL) sodium (HR=2.1, 95% CI 1.4-3.1; p=0.0002) independently predicted incident AF, whereas current use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was protective (HR=0.61, 95% CI 0.38-0.99, p=0.048). Based on the simplified risk score which included these 4 variables, annualized AF incidence rates were 0.8%, 1.8%, and 3.6% in the low (score=0), intermediate (score=1 or 2), and high-risk (score >2) groups, respectively (log rank P<0.0001; Figure). Compared to the low risk group, the intermediate and high risk groups had a 2.5-fold and 5-fold increase in the risk of incident AF, respectively (HR=2.5, 95% CI 1.5-4.0, p=0.0003 and HR=4.9, 95% CI 2.9-9.4, p<0.0001, respectively). Model discrimination was good (c-statistic=0.67; 95% CI 0.61-0.72).

Conclusions:
A simplified risk score derived from clinical and laboratory characteristics predicts incident AF in patients with HFpEF and, upon further validation, may be used clinically for risk stratification or for AF screening in high risk groups.
Figure
Abstract 15232: Lifetime Risk of Nontraumatic Lower-extremity Amputation: The Atherosclerosis Risk in Communities Study
Authors: Ding Ning , Mok Yejin , Sang Yingying , Salameh Maya , Tang Weihong , Selvin Elizabeth , Butler Kenneth R , HEISS Gerardo M , Matsushita Kunihiro
Published: May 2021

Introduction:
Nontraumatic lower-extremity amputation is a serious clinical outcome. Major risk factors include peripheral artery disease and diabetic neuropathy. Although incidence rates of amputation have been reported, no lifetime risk estimates are available.

Hypothesis:
The lifetime risk of amputation is higher in men, blacks, and those of low socioeconomic status (SES).

Methods:
In 15,744 ARIC participants aged 45-64 at baseline (1987-89), we estimated the lifetime risk of amputation through age 80 by race-sex and race-SES using Fine and Gray’s proportional subhazards model accounting for the competing risk of death. This method is optimal for time-fixed exposures and thus our primary exposures are sex and race. SES included education, annual family income, and the Area Deprivation Index linked to census tract geocoding. Non-traumatic amputation was identified from hospitalization ICD codes (e.g., 84.1, Z89.4) and related operation codes.

Results:
There were 253 non-traumatic amputations during a median follow up of 29 years. Lifetime risk of amputation at age 80 was highest in black men (4.6%), followed by black women (2.8%), white men (1.1%) and white women (0.7%) (
Figure
). Blacks of low SES showed the highest lifetime risk (4.5%). Blacks with high SES had a higher lifetime risk of amputation than whites with low SES. The pattern was consistent when we investigated each of education (≤ vs. > high school), income (< vs. ≥$25,000) and Area Deprivation Index (< vs. ≥ race-specific median), separately.

Conclusions:
In this population-based cohort 5% of black men and 3% of black women experienced a non-traumatic amputation during their lifetime, while only 1% of white men and women had a hospitalization for amputation. The lifetime risk was higher among those with lower SES in both race groups. Future public health and primary care efforts should emphasize risk factor management (e.g., diabetes and smoking) among racial minority groups and those with low SES.
Abstract 15237: Predictors of Intracranial and Gastrointestinal Bleeding in Cirrhosis With Use of Direct Oral Anticoagulants: A Large Population Based Study
Authors: Butt Muhammad U , Shah Aun R , Hamid Osama , Ghoneim Sara , Malik Maham
Published: May 2021

Introduction:
Use of Direct Oral Anticoagulants (DOACs) in patients with cirrhosis remains controversial, as the studies demonstrating safety of DOACs excluded these patients.

Hypothesis:
To determine the predictors of Intracranial and Gastrointestinal bleeding in cirrhosis with use of DOACs.

Methods:
We reviewed data from a large commercial database (Explorys IBM) that aggregates electronic health records from 26 large nationwide healthcare systems. Using systemized nomenclature of clinical medical terms (SNOMED CT), we identified adults with liver cirrhosis, intracranial and gastrointestinal bleeding. Risk factors known to be associated with bleeding such as alcohol abuse, NSAIDs, CKD and advanced age were collected. Bleeding risk with DOAC use was compared with coumadin. Univariable and multivariable logistic regression analyses were performed to investigate strongest predictors

Results:
Out of 61.4 million active adult patients in the database, 468,580 patients (0.61%) had documented cirrhosis. 9.14 % and 3.14 % of the cirrhotic patients were on DOACs and coumadin, respectively. In cirrhotic patients, there was higher composite risk of ICH or GIB if they were on DOACs (35.47% vs 21.24 % OR 2.04 [2.01-2.07]), used NSAIDs (31.15% vs 23.63% OR 1.46 [1.44-1.48]), had CKD (32.61% vs 25.04 %, OR 1.45 [1.42-1.47]), or abused alcohol (36.22% vs 23.57%, OR 1.84 [1.81- 1.87]). Risk of bleeding was higher with DOACs as compared to coumadin (35.47% vs 22.81%: p< 0.001). In Multivariable model CKD modified composite bleeding risk of ICH or GIB after adjustment for other risk factors. A cirrhotic patient on DOAC had higher risk of bleeding with CKD (OR 2.29 [(2.22-2.37)]) than without CKD (OR 1.66 [(1.63-1.69)]). This interaction was found to be statistically significant. Similar trend was noticed with use of coumadin.

Conclusions:
Major bleeding risk in cirrhosis was significantly higher with use of DOACs as compared to warfarin. This risk was highest in patients with CKD.
Abstract 15238: Cardiomyocyte Specific Pellino1 Knockout Leads to Increased Oxidative Stress, Reduced Anti-apoptotic Signaling and Cardiac Dysfunction in a Murine Myocardial Infarction Model
Authors: Pradeep Seetur R. , campbell Jacob , THIRUNAVUKKARASU Mahesh , Accorsi Diego , Palesty J. Alexander , Maulik Nilanjana
Published: May 2021

Introduction:
Ischemic heart disease is the leading cause of death in adults in the US. We have shown that overexpression of E3 ligase Pellino1 (Peli1) increased vessel density, triggered anti-apoptotic signaling, and preserved cardiac function in the infarcted myocardium. In the present study, we aimed to explore whether the loss of Peli1 function in cardiomyocytes has any effect on cardiac function using a genetically-modified murine myocardial infarction (MI) model.

Methods:
Wild type (WT) and cardiomyocyte-specific Peli1 knockout (CP1KO
-/-
) mice were divided into 4 groups [wild-type-sham (WTS), CP1KO
-/-
sham (CP1KO
-/-
S), WTMI and CP1KO
-/-
MI] to undergo either left anterior descending artery ligation or sham surgery. Phosphorylation of Mitogen-Activated Protein Kinase-Activated Protein Kinase-2 (p-MK2) and expression of VEGF, Bcl2, and cIAP2 were quantified by Western blot analysis. Cardiac function by two-dimensional echocardiography was performed at 30 days post-op to assess ejection fraction (EF), fractional shortening (FS), left ventricular internal diameter in both systole and diastole (LVIDs and LVIDd).

Results:
We observed no significant change in cardiac functions between WTS and CP1KO-/-S group. However, in MI groups, CP1KO
-/-
mice showed significant loss of systolic functions, represented by both EF (26.60%±2.340 vs. 33.46%±1.84; p<0.029, n=13) and FS (12.43%± 1.19 vs. 15.93%±0.98; n=13, p<0.03) when compared to WTMI group. Western blot analysis of heart tissue 24-hour post-MI showed a significant reduction in the expression of p-MK2 (p=0.0045) in CP1KO
-/-
group compared to WT mice. Similarly, expression of VEGF (p=0.0227), BCl-2 (p=0.0073) and cIAP2 (p=0.0483) was also found to be significantly downregulated in CP1KO
-/-
group compared to WTMI group at 4-day post-MI. We also analyzed oxidative stress marker, 3-NT, which was significantly upregulated (p=0.0001) in CP1KO mice compared to WTMI.

Conclusion:
Loss of Peli1 in cardiomyocyte results in the impairment of cardiac function along with increased oxidative stress, reduced angiogenic and survival protein expression, which suggests Peli1 plays an important role in the cardiomyocyte signaling during myocardial infarction.
Abstract 15251: Heart Failure With Preserved Ejection Fraction in Hypertrophic Cardiomyopathy With and Without Septal Myectomy
Authors: McGee Katherine , Chu Stanley , Choudhury Lubna
Published: May 2021

Introduction:
Hypertrophic cardiomyopathy (HCM) can lead to heart failure with preserved ejection fraction (HFpEF) due to left ventricular outflow tract obstruction (LVOTO). Septal myectomy can relieve LVOTO leading to resolution of HFpEF. However, some patients have persistent HFpEF even after myectomy without LVOTO. We aimed to characterize HCM patients with HFpEF post myectomy compared to those without HFpEF post myectomy and those with HFpEF and non-obstructive HCM.

Hypothesis:
There are distinct features of HCM patients with HFpEF after myectomy, no HFpEF after myectomy, and non-obstructive HCM with HFpEF.

Methods:
In this retrospective study, patients over age 18 were screened for HCM diagnosis between years 2003 and 2020, HCM was confirmed with echocardiogram and chart review. HFpEF was defined as use of loop diuretic for decongestion, with a left ventricular ejection fraction 50% or greater. Patients with septal myectomy were identified. Analysis of variance and chi-squared tests were performed.

Results:
Of 2571 patients with HCM diagnosis, there were 194 patients with HCM and HFpEF, 27 patients had HFpEF after myectomy (30%) compared to 61 patients without HFpEF after myectomy. 106 patients had nonobstructive HCM with HFpEF. A significant number of patients identifying as black or African American were in the nonobstructive HFpEF group. Hypertension was more prevalent in those with HFpEF after myectomy and non-obstructive HCM with HFpEF. Stroke was increased in the non-obstructive HCM with HFpEF (Table).

Conclusions:
30% of HCM patients develop HFpEF post myectomy, with a higher incidence of hypertension compared to those without HFpEF. Non-obstructive HCM patients, more frequently black and African American, had higher rates of hypertension and diabetes, and higher risk of ischemic stroke and mortality. These phenotypes of HCM represent an important area of investigation to assess risk for stroke and development of HFpEF after myectomy.
Abstract 15269: Baseline Relationships of Walking, Physical Activity Habits and Self-perceived Recovery After Stroke in People Engaged in a Healthy Lifestyle Program
Authors: Swank Chad , McShan Evan Elizabeth , Calhoun Stephanie , Douglas Megan , Reynolds Megan , Driver Simon
Published: May 2021

Introduction:
Recovery of walking is an important goal for people after stroke and is linked with acquiring secondary conditions deleterious to health. Our purpose was to assess the baseline relationships between walking performance, physical activity habits and self-perceived recovery after stroke in people engaged in a healthy lifestyle program.

Hypothesis:
We hypothesized that walking performance would be strongly related to self-reported stroke recovery and physical activity habits.

Methods:
Community dwelling adults at least 12 months post-stroke with a body mass index (BMI) of 25 or greater were recruited to participate in a healthy lifestyle program adapted for people with stroke. Baseline measures of walking performance [10-meter walk test (10MWT); 6-minute walk test (6MWT)] and self-reported outcomes [Self-Report Habits Index (SRHI); Stroke Impact Scale (SIS)] were correlated.

Results:
Adults (34 male, 31 female; 64.6% scored as having some disability on the Modified Rankin Scale) aged 57.9±12.8 years with a BMI of 33.0±5.9 and median of 3 years post-stroke participated. 10MWT walking speed was 1.0±0.4m/s and 6MWT distance walked was 343.3±132.3m. SRHI physical activity scores of 4.6±1.7 (above average habit formation; scale = 1 - 7) and SIS subscales ADL/IADL and mobility normed scores of -0.1±0.7 and -1.3±0.8 respectively, and perceived recovery of 70.9±16.9% were reported. The 10MWT was significantly and moderately correlated with SIS ADL/IADL (r=0.48; p<0.001) and mobility (r=0.41; p<0.001), but weakly with SIS perceived recovery (r=0.34; p<0.01) and SRHI physical activity (r=-0.32; p<0.01). The 6MWT was significantly and moderately correlated with SIS ADL/IADL (r=0.48; p<0.001) and mobility (r=0.47; p<0.001), but weakly with SIS perceived recovery (r=0.33; p<0.01) and SRHI physical activity (r=-0.33; p<0.01).

Conclusions:
Walking performance among our participants post-stroke was consistent with community dwelling adults, but only somewhat related to their perception of recovery of function and mobility. Additional factors beyond perceived recovery likely contribute to walking abilities post-stroke.
Abstract 15270: Coronary Plaque Natural History Displays Marked Longitudinal Heterogeneity Along the Length of Individual Coronary Plaques
Authors: Wentzel Jolanda J , Papafaklis Michail I , Antoniadis Antonios , Takahashi Saeko , Cefalo Nicholas V , Cormier Michelle , Saito Shigeru , Coskun Ahmet U , STONE Peter H
Published: May 2021

Introduction:
Plaque natural history is related to local shear stress, and shear stress has been shown to be heterogeneously distributed along the length of individual plaques. We investigated the longitudinal spatial heterogeneity of plaque progression/regression/quiescence in human coronary arteries.

Methods:
591 coronary arteries from 302 patients with coronary disease who presented with an acute coronary syndrome from the PREDICTION study were investigated for local plaque progression/regression/quiescence patterns in non-culprit plaques after 6-10 month FU. Arterial geometry was derived from angiography/IVUS-based vascular profiling and reported in 3 mm segments. Plaques were defined as >3 consecutive segments with maximal wall thickness>0.5 mm. Plaque progression was defined as >5% increase, regression as <-5% decrease, and quiescence as no change in plaque burden (plaque area/ total vessel area * 100%).

Results:
5658 3mm-segments of 661 plaques were analyzed. Plaque burden changes ranged from -22% to +20%. Among all plaques, 56% showed segments with plaque progression, 60% with regression and 96% with quiescence. On average, 17% of the plaque length displayed plaque progression, 20% regression and 63% quiescence. The presence and number of natural history features (progression, regression, quiescence) within the individual plaques were significantly related to plaque length using logistic mixed model regression analysis (figure).

Conclusions:
Coronary plaque natural history is extremely heterogeneous along the length of an individual plaque. These observations may explain why revascularization of a focal severe obstruction in the ISCHEMIA trial did not affect clinical outcomes, since remaining high-risk plaque up- or down-stream from the revascularization may have led to future cardiac events.
Abstract 15282: Right Ventricular Echocardiographic Analysis in the Critically Ill COVID-19 Population
Authors: Jaglan Akshar , Roemer Sarah , Perez Moreno Ana C , Salinas Pedro D , Khandheria Bijoy K
Published: May 2021

Introduction:
Coronavirus disease 2019 (COVID-19), has rapidly spread around the world and reached a pandemic level. The utility and benefit of echocardiographic analysis in this patient population has just started to be documented in the literature. We use this study to show the benefits of analyzing right ventricular (RV) function in this patient population.

Methods:
We assessed RV systolic function in 22 (mean age 63.5±4 years; 73% male) patients admitted to the ICU who tested positive for COVID-19. The transthoracic echocardiograms performed on the critically ill COVID-19 patients were focused studies done in supine position. Right ventricular free wall strain (RVFWS) was analyzed on proprietary software (EchoPac 202, GE Vingmed Ultrasound, Horten, Norway). RV systolic dysfunction was classified as tricuspid annulus peak systolic velocity (S’) <9.5 cm/s or RVFWS <-20%.

Results:
All 22 patients had either an S’ or RVFWS measurement; 20 of them had an observation for S’ and 16 had an observation for RVFWS. Median RVFWS among all patients was reduced at -18.5%. At the time of this writing, 14 of the 22 patients were being treated in the ICU or had died; median RVFWS in this subgroup was reduced at -17.5% and S’ at 12 cm/s. The 8 patients who transferred out of the ICU had a median RVFWS of -23.5 and S’ of 16 cm/s. Of the 10 patients classified as having RV dysfunction, 9 were due to RVFWS <-20% and 1 to S’ of < 9.5. Excluding patients who passed away, RV dysfunction was associated with a longer median ICU stay (21.5 days [interquartile range {IQR} 13-30] vs 9 days [IQR 5.5-16.5]; p=0.03).

Conclusions:
Of the 22 patients included in the study, currently 5 have died, 9 remain intubated in critical condition in the ICU, and 8 have been transferred to the medicine floor. In conclusion, focused, rather than point-of-care, ultrasound should be utilized to analyze RV function as there is clear evidence that RVFWS is correlated with longer ICU stay and poorer prognosis.
Abstract 15290: 4D-flow MRI Intracardiac Flow Hemodynamic Patterns Can Phenotype Different Subtypes of Pulmonary Hypertension
Authors: Ross Lexie K , Barker Alex J , Frank Benjamin S , Hunter Kendall S , Morgan Gareth , Mitchell Max B , IVY Dunbar D , Fenster Brett E , Shafer Michal
Published: May 2021

Introduction:
Idiopathic Pulmonary Arterial Hypertension (PH-Type I) and PH due to pulmonary disease (PH-Type III) arise from different pathophysiologic processes, yet they both culminate in increased right ventricular (RV) afterload and eventual RV failure. Previous work has demonstrated that 4D-Flow MRI-derived intracardiac vorticity (ω) correlates with markers of ventricular interdependency and diastolic dysfunction in PH. However, no investigation has attempted to use both ω and standard markers of ventricular function to phenotype PH subgroups.

Hypothesis:
4D-Flow MRI can detect differences in diastolic dysfunction that make it possible to phenotype patients with Type I and Type III PH.

Methods:
Type I PH patients (n=12, mean age 61yrs), Type III PH patients (n=15, mean age 63yrs), and healthy controls (n=10, mean age 58yrs) underwent standard cardiac MRI as well as 4D-Flow MRI to determine RV intracardiac flow markers including early (ω-E) and late (ω-A) diastolic vorticity. Standard MRI-based RV and LV size and function markers were also collected.

Results:
ω-E was decreased in the Type I PH group compared to the Type III PH group (P=0.035) and to controls (P<0.001). There was no difference in ω-E between the Type III group and controls (P=0.216). RVEF was decreased in both the Type I (P<0.001) and Type III (P=0.012) group compared to controls. There was no difference in RVEF between the Type I and Type III groups (P=0.917). RVEDV was increased in both the Type I (P=0.008) and Type III (P=0.006) groups compared to controls. No significant differences were noted between groups when assessing (ω-A) and other RV or LV standard volume and functional indices.

Conclusion:
Our results indicate that 4D-Flow MRI can distinguish among different PH subtypes using intracardiac diastolic vorticity. Comparative studies with standard echocardiography and catheterization are necessary to assess the sensitivity of 4D-Flow MRI to detect diastolic dysfunction.
Abstract 15297: Discovery and Preclinical Optimization of Selective ABCA1 Inducers as Multifunctional Therapeutic Candidates
Authors: Lewandowski Cutler , Khan Md. Wasim , Ben Aissa Manel , Layden Brian , Thatcher Gregory
Published: May 2021

Introduction:
Reduced expression of cholesterol transporter ABCA1 is critical in pathogenesis of type 2 diabetes (T2D) and related conditions, such as cardiovascular disease (CVD) and Alzheimer’s disease (AD). Thus, increasing ABCA1 represents a novel therapeutic strategy for these conditions. However, prior drug development efforts have achieved limited success at increasing ABCA1 (controlled by liver X receptor [LXR] β) while avoiding unwanted liver triglyceride production (through LXRα via transcription factor SREBP1c).

Hypothesis:
We hypothesized that phenotypic screening for selective ABCA1 inducers followed by medicinal chemistry optimization would bypass the isoform selectivity issues encountered in traditional target-based drug discovery and enable development of lead therapeutic candidates with preclinical efficacy and safety.

Methods/Results:
We screened 20k compounds for ABCA1 and SREBP1c-linked luciferase activity, followed by qPCR to validate and prioritize selective ABCA1-inducing hits. We synthesized ~70 structural analogs of the best hit, achieving substantial EC
50
(4.5 μM to 270 nM) and E
max
(3.5-fold to 6.0-fold vs. vehicle) improvements in ABCA1 luciferase assay while maintaining selectivity against SREBP1c. Direct binding assays confirmed selectivity for LXRβ vs. LXRα, corroborating cell-based data. Lead compounds enhanced cellular cholesterol efflux, reduced inflammation
in vitro
, and attenuated high-fat diet (HFD) induced weight gain, insulin resistance, and inflammation in mice. Metabolomics analysis revealed that our lead compound corrected HFD-induced perturbations in liver glucose and fatty acid synthesis. Finally, side effects associated with published LXR agonists - liver steatosis and neutropenia - were not observed with our compound.

Conclusions:
We established a platform to develop selective ABCA1 inducers as drug candidates. Via this platform, we identified a safe and efficacious lead compound for T2D. Our study also represents the first report of an LXR agonist characterized by metabolomics - a powerful tool to complement biochemical readouts. Continued optimization to improve pharmacokinetic parameters, plus evaluation in CVD and AD models, is ongoing.
Abstract 15303: Dimethylarginine Dimethylaminohydrolase-1 is Not Involved in Chronic Hypoxic Pulmonary Hypertension and Right Ventricular Hypertrophy in Mice
Authors: Hannemann Juliane , Glatzel Antonia , Hillig Jonas , Zummack Julia , Boeger Rainer H
Published: May 2021

Introduction:
Chronic hypoxia causes persistent pulmonary vasoconstriction and leads to pulmonary hypertension and right ventricular hypertrophy. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis; its level increases in hypoxia concomitantly with reduced activity of dimethylarginine dimethylaminohydrolases (DDAH-1 and DDAH-2), the enzymes metabolizing ADMA. DDAH knockout models may therefore help to understand the pathophysiological roles of this enzyme and its substrate, ADMA, in the development of hypoxia-associated pulmonary hypertension.

Hypothesis:
We hypothesized that DDAH1 knock-out mice have an attenuated hypoxia-induced elevation of ADMA and reduced right ventricular hypertrophy.

Methods:
DDAH1 knock-out mice (KO) and their wild-type littermates (WT) were subjected to normoxia (NX) or hypoxia (HX) during 21 days. We measured ADMA concentration in plasma, DDAH1 and DDAH2 expression in the lung, right ventricular hypertrophy by the Fulton index, cardiomyocyte hypertrophy by dystrophin staining of heart tissues, and muscularization of pulmonary arterioles by CD31 and α-actin staining of lung sections.

Results:
DDAH1 KO mice had higher ADMA concentration than WT under NX (2.31±0.33 μmol/l vs. 1.20±0.17 μmol/l; p < 0.05). ADMA significantly increased in WT-HX (to 1.74±0.86 μmol/l; p < 0.05 vs. normoxia), whilst it did not further increase in KO-HX (2.58±0.58 μmol/l; p = n.s.). This was paralleled by a 38±13% reduction in DDAH1 mRNA but not DDAH2 mRNA expression, and reduced DDAH protein expression. We observed right ventricular hypertrophy under hypoxia in both, WT and KO mice, with no significant differences between both genotypes. Further, cardiomyocyte hypertrophy and pulmonary arteriolar muscularization were significantly increased by hypoxia, but not significantly different between WT and KO mice.

Conclusions:
We conclude that chronic hypoxia causes an elevation of ADMA, which impairs NO production and leads to endothelial dysfunction and vasoconstriction. Downregulation of DDAH expression and activity may be involved in this; however, knockout of DDAH1 does not modify the pathophysiological changes in remodeling of the pulmonary vasculature and the right ventricle.
Abstract 15308: Psoriasis Does Not Worsen Outcomes of Patients Admitted for Atrial Fibrillation: Analysis of the National Inpatient Sample
Authors: Edigin Ehizogie , Eseaton precious O , Asemota Iriagbonse R , Akuna Emmanuel , Shaka Hafeez , Ojemolon Pius E
Published: May 2021

Introduction:
Studies have shown that psoriasis increases the risk of atrial fibrillation (AF). However, it is unclear if co-existing psoriasis worsens outcomes in AF hospitalizations. This study aims to compare the outcomes of patients primarily admitted for AF with and without a secondary diagnosis of psoriasis.

Methods:
Data were abstracted from the National Inpatient Sample (NIS) 2016 and 2017 Database. NIS is the largest inpatient hospitalization database in the United States. The NIS was searched for hospitalizations for adult patients with AF as principal diagnosis with and without psoriasis as secondary diagnosis using ICD 10 codes. The primary outcome was inpatient mortality. Hospital length of stay (LOS), total hospital charges, odds of undergoing ablation, pharmacological, and electrical cardioversion were secondary outcomes of interest. Multivariate logistic and linear regression analysis was used accordingly to adjust for confounders. STATA software was used to analyze the data.

Results:
There were over 71 million hospitalizations in the combined NIS 2016 and 2017 database. Out of 821,630 hospitalizations for AF, 4,490 (0.55%) had Psoriasis. Hospitalizations for AF with psoriasis had similar inpatient mortality [0.78% vs 0.92%, AOR 0.95, 95% CI (0.44-2.04), P=0.895], total hospital charge [$41,869 vs $39,145, P=0.572] and longer LOS [3.72 vs 3.37 days, P=0.023] compared to those without psoriasis. Odds of undergoing ablation [5.0% vs 4.2%, AOR 1.12, 95% CI (0.82-1.52), P=0.481], pharmacologic cardioversion [0.11% vs 0.38%, AOR 0.29, 95% CI (0.04-2.10), P=0.219] and electrical cardioversion [19.2% vs 17.5%, AOR 0.99, 95% CI (0.83-1.19), P=0.930] were similar in both groups.

Conclusion:
Hospitalizations for AF with psoriasis had longer LOS compared to those without psoriasis. AF hospitalizations with psoriasis however had similar inpatient mortality, total hospital charges, odds of undergoing ablation, pharmacologic and electrical cardioversion compared to those without psoriasis.