bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13478: Cardiac Magnetic Resonance Imaging Identifies Cardiac Disease in Limb-Girdle Muscular Dystrophy in Previously Low Risk Mutations
Authors: Vickery Selina , Mendell Jerry R , Lehman Kelly , Hor Kan N
Published: April 2022

Introduction:
Limb-Girdle Muscular Dystrophies (LGMD) are an inheritable group of genetic disorders primarily involving progressive weakening and atrophy of the pelvic or shoulder girdle musculature with potential cardiac dysfunction. Prior reports stratified frequency of cardiac disease based on genetic mutations. The general incidence of cardiac muscle involvement in LGMD is variable depending on genetic factors and carry important indications for clinical management. Cardiac magnetic resonance imaging (CMR) is increasingly used in dystrophinopathies and determining management. There is limited CMR data in adult LGMD patients and fewer reports in younger patients.

Hypothesis:
Therefore, we sought to determine the extent of cardiac involvement based on genetic risk of cardiomyopathy.

Methods:
This is a retrospective review of LGMD patients followed at our institution who underwent CMR assessment. Patients stratified into Group A (high incidence of cardiomyopathy; LGMDs 1B, 2E, 2F and 2I) and Group B (rare or no reported cardiomyopathy; LGMDs 1A, 1C, 2A, 2B, 2C, 2D, 2G, 2H, 2J) with CMR studies were assessed for presence of cardiac scar defined as late gadolinium enhancement (LGE) and LVEF for each subject.

Results:
41 subjects were identified with average age of 21.3±11.5 years (range 6-50) with normal LVEF 58±12.1% and 12/41 (29.3%) with LGE with the youngest patient age 12.4 years. Group A included 14/41 (34%) and 27/41 (66%) were in Group B. Group A had higher incidence of LGE 6/14(42.9%) with preserved LVEF of 58.2±11% compared to Group B with 6/27 (22.2%) with no difference in LVEF of 55.7±16.4% (p = 0.5). When stratified by LGE status, the LGE-positive group was older at 26.4±11.9 years and had preserved LVEF of 61.9±11.1% versus LGE-negative group of 19.1±10.9 years (p = 0.03) with abnormal LVEF of 49.4±9.5% (p =0.0008).

Conclusions:
This is the largest study of CMR in LGMD patients, confirming presence of cardiac disease by LGE in the high risk group. Surprisingly, nearly 25% of the low risk mutations have evidence of LGE. Abnormal LGE predicted abnormalities in LVEF in both Group A and Group B. Management of LGMD patients should include CMR even in low risk population. Ongoing data collection may reveal disease cluster in previous low risk groups.
Abstract 13526: Left Atrial Appendage Emptying Velocity is a Predictor of Atrial Fibrillation Recurrence in Patients Undergoing Catheter Ablation
Authors: Thotamgari Sahith Reddy , Ahmad Javaria , Sheth Aakash , Bawa Danish , Thevuthasan Sindhu , Dominic Paari
Published: April 2022

Introduction:
Low left atrial (LA) voltage is known to predict Atrial Fibrillation (AF) recurrence after catheter ablation (CA); however, its measurement involves invasive electrophysiology study (EPS). Left Atrial Appendage (LAA) emptying velocities are routinely measured during pre-procedural Transesophageal Echocardiography (TEE). We sought to assess the association between LAA velocities and AF recurrence after CA.

Hypothesis:
Pre-procedural LAA emptying velocity is a predictor of AF recurrence in patients undergoing CA.

Methods:
A total of 263 consecutive patients who underwent CA for AF between 2014 and 2020 were included. Baseline clinical characteristics and echocardiographic data of the patients were obtained by chart review. LAA emptying velocities were obtained from TEE. LA voltage was obtained during the EPS. Chi-square test and nominal logistic regression were used for statistical analysis. A sensitivity of 80% on the ROC curve was used for determining LAA velocity cut-off.

Results:
Mean patient age was 60.8±10.9; 34% were female. Mean LAA emptying velocity was 48.0±20.4. Mean average total voltage (Vavg) of LA was 1.58±1.05. There was a significant positive linear correlation between LAA velocity and LA Vavg (p=0.004*). A total of 68 (26%) patients had recurrence after CA. Patients with lower LA Vavg had increased AF recurrence compared to patients with higher LA Vavg (p=0.004*). In the multivariable model, after adjusting for HTN, CAD, HFrEF, and DM, LAA emptying velocity of ≥52.3 was associated with decreased AF recurrence post-ablation (OR 0.31; 95% CI 0.15-0.66; p = 0.002*). There were 190 (73%) patients in normal sinus rhythm during EPS mapping, and sensitivity analysis of these patients showed that LAA velocity ≥52.3 remained associated with decreased AF recurrence (OR 0.35; 95% CI 0.15-0.82; p = 0.01*).

Conclusions:
LAA emptying velocity measured during pre-procedural TEE can serve as a predictor of AF recurrence in patients undergoing CA.
Abstract 13529: Efficacy and Safety of Direct Oral Anticoagulants and the Watchman™ Atrial Appendage Closure Device in Non-Valvular Atrial Fibrillation: A Network Meta-Analysis of Randomized Controlled Trials
Authors: Maqsood Muhammad Haisum , Brown David L , Gleva Marye
Published: April 2022

Introduction:
The efficacy and safety of the Watchman
TM
(WM) left atrial appendage closure device in atrial fibrillation (AF) was determined in randomized controlled trials (RCTs) with warfarin treatment of the control group. Direct oral anticoagulants (DOAC) have largely superseded warfarin in contemporary clinical practice for stroke and thromboembolism prevention in AF. Network meta-analysis (NMA) allows integration of direct and indirect evidence in evaluating relative effects of three or more interventions. Because there are no direct comparisons of WM with DOACs, we performed a NMA to compare the efficacy and safety of WM to DOACs in patients with AF.

Methods:
We searched PubMed, EMBASE, and Google Scholar from January 1990 until March 2021 for prospective RCTs that evaluated the efficacy and safety of warfarin, WM, and DOACs in pairwise comparisons of patients with AF. The co-primary outcomes of interest were i) thromboembolic events including stroke, and ii) major bleeding events. Comparative outcomes were assessed by odds ratios (OR) with 95% confidence intervals (CI). Stata version 17.0 software was used for the analysis.

Results:
A total of 60,652 patients with AF enrolled in 10 RCTs were included. There was no difference in stroke or thromboembolism prevention between WM and DOAC [OR =1.04 (95% CI: 0.61-1.75; 9 trials) (Figure panel A). Similarly, there was no significant difference in major bleeding risk between WM vs DOAC [OR = 1.87 (95% CI: 1.0 – 3.52] (Figure panel B). No significant heterogeneity or publication bias was found.

Conclusions:
Based on this NMA, WM appears to provide no benefit in prevention of thromboembolism/stroke compared to DOAC in patients with AF. However, a reduction in the risk of major bleeding with WM cannot be ruled out. Future RCTs are necessary to better quantify the risk and benefit of WM compared to DOAC for patients with AF.
Abstract 13531: Coronary-Cameral Fistulae Causing Coronary Steal Syndrome Inducing Polymorphic Ventricular Tachycardia
Authors: Bigham Thomas E , Bhargava Ankit , Chaku Akshay , Jokhadar Maan
Published: April 2022

Background:
Coronary-cameral fistulae are rare, and usually benign, anomalous connections between coronary artery and cardiac chambers. These fistulae are rarely large enough to cause ischemia, arrhythmia, and heart failure.

Case:
A 49 year-old female with a complicated medical history including numerous systemic arteriovenous malformations, high output heart failure, hypertrophic cardiomyopathy with MRI proven myocardial fibrosis, recurrent monomorphic ventricular tachycardia (VT), defibrillator placement, with recent VT ablation and sympathectomy presented to the coronary care unit for recurrent monomorphic VT. During her CCU course, this patient developed a distinctly different, incessant polymorphic VT with progression to ventricular fibrillation (VF).

Decision-making:
The patient was started on a procainamide infusion in addition to her amiodarone infusion. Her device pacing rate was increased to improve systemic perfusion. Unfortunately, this appeared to worsen the burden of polymorphic VT. She underwent emergent cardiac catheterization, which demonstrated multiple coronary cameral fistulae arising from all three major coronary vessels with brisk flow into the left ventricular cavity, concerning for coronary steal syndrome causing ischemia. To improve coronary diastolic filling time, the pacing rate was decreased. The largest fistula, the distal PDA to left ventricle, was embolized. She remained free of polymorphic VT for 13 days, but ultimately died due to complications of aspiration pneumonia with septic shock and multiorgan system failure.

Conclusion:
Acute myocardial ischemia is a common cause of polymorphic ventricular tachycardia. In this medically complicated patient with history of monomorphic VT suspected secondary to myocardial scar, her polymorphic VT was likely precipitated by the coronary-cameral fistulae causing coronary steal syndrome with improvement of her polymorphic VT after embolization and slowing heart rate with ischemia reduction.
Abstract 13534: Plasma Apolipoprotein C3 is Negatively Associated With High Lipoprotein(a) Plasma Levels in Healthy Volunteers
Authors: Matveyenko Anastasiya , Matienzo Nelsa , Thomas Tiffany , Ramakrishnan Sekhar , Seid Heather , Ginsberg Henry N , Reyes-soffer Gissette
Published: April 2022

Introduction:
ApoliproteinC3 (apoC3) is a small (~8.8kDa) protein, made in the liver. It is an inhibitor of lipoprotein lipase as well as the uptake of triglyceride (TG) rich lipoproteins and remnants by the liver. Overexpression contributes to atherosclerosis by increasing plasma concentration of TG-rich lipoproteins. A recent study reported the presence of apoC3 on lipoprotein(a) [Lp(a)] particles in subjects with mild to moderate aortic stenosis. Lp(a) is an apoB100 containing lipoprotein with apo(a) covalently bound and is a causal factor of ASCVD. Our goal was to investigate relationships between apoC3 and Lp(a) in a healthy population.

Methods:
We analyzed data from 39 healthy subjects who completed studies of lipoprotein metabolism at the Columbia University Irving Medical Center. Subjects were 18 - 75 years old, and 44% were female. Twenty were Black, 9 Hispanic, 8 White, and 2 mixed race. Lipids (total Cholesterol (C), TG, HDLC, LDLC) were measured by an automatic analyzer. Plasma apoC3, apoB100 and Lp(a) levels were measured via validated ELISA assays. Lp(a) particles were isolated from plasma by immunoprecipitation (IP) with a monoclonal antibody and Western blots were performed.

Results:
We did not find an association between plasma Lp(a) and apoC3 levels. In a sub-group analysis of participants (N=15), with Lp(a) levels >100nmol/L, we found a significant negative association between apoC3 and Lp(a) plasma concentrations (R = -0.58, p=0.018). Based on the Western blots and ELISA analysis, we see an interaction between Lp(a) (apo(a) and apoB100 intact) and apoC3. There seem to be some differences in the Lp(a) and apoC3 interaction based on Lp(a) plasma concentration.

Conclusion and Future Direction:
In healthy subjects, there is no association of apoC3 with Lp(a) plasma levels. In a subset of subjects (high Lp(a)), we observed an association with apoC3 plasma levels. Our small data set suggests possible distinct roles for apoC3 in healthy individuals with high Lp(a) level. ApoC3 may be associated with specific circulating isoform sizes of Lp(a). Future studies will focus on analysis of larger cohorts and examining lipid composition in the isolated particles.
Abstract 13536: Snai1 Knockdown Rescues Pulmonary Hypertension-Induced Right Ventricular Failure in Rats by Inhibiting Endothelial-to-Mesenchymal-Transition and Fibrosis via LOXL2 Dependent-H3K4 Methylation Status Remodeling
Authors: Banerjee Somanshu , Clark Varina R , HONG JASON , Park John , Razee Asif , Umar Soban
Published: April 2022

Introduction:
Pulmonary hypertension (PH)-induced RV failure (PH-RVF), a significant prognostic determinant, is characterized by RV endothelial-to-mesenchymal transition (EndMT) and fibrosis. The regulatory control mechanisms of RV EndMT and fibrosis remain unclear. The action of transcription factor Snai1 in EndMT is proposed to be mediated
via
LOXL2 recruitment, their nuclear co-translocation and subsequent histone-H3K4 methylation status remodeling.

Hypothesis:
PH-RVF is associated with EndMT and fibrosis, governed by TGFβ1-Snai1-LOXL2 axis. Targeting Snai1 could serve as a novel therapeutic strategy for PH-RVF.

Methods:
Male rats received s.c. Monocrotaline (MCT, 60mg/kg, n=7; 30-days) or Sugen (20mg/kg, n=7; 3-wk hypoxia+2-wk normoxia) or PBS (CTRL, n=7). For Snai1-KD, MCT rats received siSnai1 (n=6; 5nM every 3-4d, IV) or scramble (n=7) from day 14-30. Echo and cath were performed. RVs were stained for fibrosis and EndMT. RV RNASeq and PCR validation performed. Human RVs (CTRL n=3; PAH n=7) were stained with trichrome and Snai1/LOXL2. Snai1-KD was performed on human coronary artery endothelial cells (HCAECs) under hypoxia+TGFβ1 (72h). 21 different Histone-H3 modifications were assessed in rat RVs. Values are mean±SD.

Results:
MCT and SuHx rats had increased RVSP and Fulton Index (FI) and decreased RVFAC (all
p
<0.001). RNASeq showed EndMT as the top upregulated pathway. RV EndMT, fibrosis and myofibroblast transition were increased in MCT and SuHx rats and PH-RVF patients. RV TGFβ1, Snai1 and LOXL2 were increased in MCT and SuHx. Snai1+LOXL2 colocalized in nucleus in MCT and SuHx rats and human RVs. Snai1-KD showed decreased Snai1 expression (~3-fold), RVSP (45±2 mmHg;
p
<0.05), FI (0.41±0.01;
p
<0.05) and increased RVFAC (24±0.01; p<0.05). Snai1-KD resulted in decreased RV LOXL2, EndMT and fibrosis. RNASeq showed EndMT as top downregulated pathway and decreased fibrotic DEGs. Only RV H3K4me2 upregulation was reversed by Snai1-KD. Snai1-KD inhibited hypoxia+TGFβ1-induced EndMT in HCAECs by decreasing Snai1+LOXL2 expression and co-localization.

Conclusions:
PH-RVF is associated with EndMT, fibrosis and H3K4me2 status remodeling mediated
via
TGFβ1-Snai1-LOXL2 axis. Targeting Snai1 is a novel therapeutic strategy for PH-RVF.
Abstract 13538: Impact of Autophagy Modulation on Apoptosis in Chemotherapy-Induced Cardiac Toxicity
Authors: Boukhalfa Asma , Dawn Meola M , LaMastro Joey , Robinson Sally , Meng Lin , Weng Sydney , Robinson Nicholas , Martin Greg , Sosnovik David E , Blanton Robert M , Yang Vicky , Chen Howard H
Published: April 2022

Background:
Cardiotoxicity due to chemotherapy remains a challenge. Cardioprotective interventions have not slowed the progression to heart failure. Cardiomyocyte (CM) death can be attributed to autophagy impairment during chemotherapy-induced toxicity. We hypothesize that autophagy activation can be a viable cardioprotective strategy.

Methods:
H9C2 rat cardiac myoblasts and cardiac slices generated from euthanized dog hearts were treated with 5-50μM doxorubicin (Dox) +/- autophagy activators for 24 hours. Annexin V (Anx) and TUNEL detection of apoptosis, MTT assay of cell viability, and western blots were performed. C57Bl6 mice were challenged with either single Dox (15 mg/kg i.p.), or repeated doses (4 mg/kg i.p., weekly, 5x) +/- 24-hour pre-starvation. Cardiac function was assessed by echo.

Results:
Dox significantly increased H9C2 apoptosis, rescued by rapamycin (Fig. A). Autophagy induction by phosphatidylinositol-3-phosphate (Pi3P) restored autophagic flux via downregulating autophagy-inhibitory Rubicon (Fig. B). Autophagy stimulation by Pi3P, statins, or starvation significantly reduced H9C2 apoptosis and improved viability (Fig. C-E), but not in human cancer cells. Single high Dox dose in mice markedly increased CM apoptosis by 24 hours, attenuated by pre-starvation without perturbing Dox retention in the heart (Fig. F). In chronically treated Dox mice, starvation before each Dox dose improved cardiac function and survival (Fig. G-H). Viable dog cardiac slices generated (Fig. I-J) exhibited preserved autophagic flux (Fig. K). Dox (5μM, 30-min exposure) induces autophagy blockade at 24 hours leading to apoptosis (Fig. L). Autophagy restoration by rapamycin reduced apoptosis in cardiac slices but not primary canine cancer cells (Fig. M).

Conclusions:
Autophagy restoration via modulating Rubicon exerts anti-apoptotic effects in murine and canine CMs, but not in cancer cells, potentially translatable to impact cardio-oncology treatment.
Abstract 13540: Quantifying the Respiratory Effort From Right Heart Catheterization Can Assist in Evaluating Heart Failure Severity
Authors: Markovitch Noa , Rispler Shmuel , Feld Yair , Solomonica Amir , Yalonetsky Sergey , Musallamis Anees , Roguin Ariel , Kerner Arthur , Landesberg Amir
Published: April 2022

Introduction:
Right heart catheterization (RHC) provides objective assessment of heart failure (HF) severity. However, it is strongly affected by respiratory fluctuations, therefore various methods were suggested to correct these fluctuations. In contrast,
we hypothesized
that measurement of the respiratory effort in addition to the standard indices provides additional valuable information. Moreover, it can assist in the interpretations of the standard indices.

Methods:
We simultaneously measured the hemodynamic and respiratory indices in HF patients undergoing RHC. The pulmonary wedge pressure (PCWP) is modulated by the changes in the intrathoracic pressure. The latter is determined by the respiratory effort. To quantify the respiratory effort, the PCWP was decomposed into cardiac and respiratory waves. The respiratory effort (P
RESP
) was defined as the peak to peak amplitude of the respiratory wave that modulated the PCWP.

Results:
HF patients (N=45) exhibited a high P
RESP
of 9.1±5.3 mmHg, ~3.5-fold higher than the reported normal respiratory modulations, while they are lying and at rest [Range: from 2.0 mmHg to 23.3 mmHg]. In some patients the P
RESP
exceeded the amplitude of cardiac `a` and `v` waves. The difference between end expiratory PCWP (PCWP
EE
) and mean PCWP increased linearly with P
RESP
, by slop of 0.380±0.001 (R
2
= 0.76, p<0.001). The end expiratory PCWP rose with P
RESP
, by 0.68±0.05 mmHg for every 1 mmHg of P
RESP
(p<0.01). Interestingly, identical changes in the PCWP with P
RESP
were obtained in all the patients, independently of the HF etiology. The P
RESP
sheds light on the severity of dyspnea. It enables simple and precise evaluation of the PCWP
EE
from regular breathing. Lung congestion severity is determined by the transmural gradient between the intravascular pressure and the tissue surrounding pressure. Correction for P
RESP
yields more accurate evaluation of this transmural pulmonary vascular pressure.

Conclusions:
P
RESP
provides additional essential dimension on the severity of dyspnea and HF. It simplifies the measurement method and enables to derive the PCWP
EE
. The latter deviates from the mean PCWP in cases of severe dyspnea. It assists in evaluating the real transmural pulmonary vascular pressure.
Abstract 13563: Acute Effects of Inspiratory Loads and Pursed Lips Breathing on Non-Linear Heart Rate Variability in Young Health Subjects
Authors: Sa Joceline , Resqueti Vanessa , Dias Cibele Therezinha , Dias Fernando A , Fregonezi Guilherme
Published: April 2022

Introduction:
Inspiratory muscle loads and breathing exercises are recognized tools used to improve the rehabilitation process.

Hypothesis:
Inspiratory loads and pursed lips breathing have different effects on the heart rate variability in young healthy subjects.

Methods:
Twenty-nine subjects were studied (15 male), aged 22.6 ± 2.9 years and BMI: 22.8 ± 2.7 Kg/m
2
, without respiratory and cardiac-related diseases. Subjects were randomized into three experimental groups: 20% PImax inspiratory load (IL
20%group
), 50% inspiratory load (IL
5
0%
group
), and pursed lips breathing (PLB
group
). Heart rate variability was measure before and while subjects breathing using different load's intensity or pursed lips breathing technique.

Results:
A significant change in autonomic balance was found, with greater parasympathetic modulation on the heart during pursed lips breathing and increased sympathetic activity during moderate inspiratory load (Table 1).

Conclusion:
Acute effects of moderate inspiratory load improves sympathetic activation and may influence the behavior of heart rate when used in patients with arrhythmias or other heart clinical conditions. Also, pursed lips breathing can be considered as a breathing exercise that could be promoter the cardioprotective effect. in memoriam
Fernando Henrique de Macedo
Abstract 13573: Prediction of Culprit Lesions in Acute Coronary Syndrome Based Upon Myocardial Mass At-Risk From Coronary CT Angiography
Authors: Malkasian Shant , Shadmani Ghazal , Earls James , Min James K , Molloi Sabee
Published: April 2022

Introduction:
Stratifying patients with coronary artery disease (CAD) remains challenging. Assessing CAD using myocardial mass at-risk may help identify patients at higher risk of acute coronary syndrome.

Hypothesis:
This study investigated whether quantitative myocardial mass at-risk (MMAR) can improve prognostication of future culprit coronary lesions at the time of acute coronary syndrome (ACS) events.

Methods:
From the multicenter, international ICONIC study, 49 patients suspected of coronary artery disease (CAD) going coronary CT angiography imaging (CCTA) were followed to the occurrence of the first ACS. At the time of ACS, culprit lesion was adjudicated by invasive coronary angiography by a group of cardiologists blinded to the previously acquired CCTA. MMAR was calculated for each lesion using the minimum-cost path technique, a previously validated method for calculating myocardial perfusion territories. Left ventricle myocardial segmentation and coronary centerline extraction was performed and used to calculate MMAR distal to all identifiable culprit and non-culprit coronary lesions.

Results:
In the study sample, 243 coronary lesions were identified on CCTA (194 non-culprit lesions; 49 culprit lesions). The mean MMAR, as a percentage of total left ventricle myocardial mass, for all lesions was 24.6±12.4%. The mean MMAR was 23.1±12.5% and 30.3±10.3% for non-culprit and culprit lesions, respectively (p<0.05). Receiver operating characteristic curve analysis was performed to determine the value of MMAR in predicting a culprit lesion, with an area-under-the-curve analysis for MMAR predicting a culprit lesion of 0.68.

Conclusions:
MMAR is larger for lesions that will versus will not become culprit at the time of future ACS. The addition of MMAR in the assessment of CAD on CCTA may help stratify the risk of individual coronary lesions.
Abstract 13575: Conversion of a Face-to-Face Educational Intervention to Electronic Delivery Offers Increased Access to Women With a History of Acute Coronary Syndrome
Authors: Davis Leslie L , Teng Chiao-hsin , Tippey Kathyrn
Published: April 2022

We previously tested a face-to-face individualized educational intervention designed to improve symptom recognition in women who had recently experienced an acute coronary syndrome event. To increase accessibility to women in rural communities we converted the face-to-face intervention to a digital format including a responsive symptom monitoring diary. We implemented user experience tools to optimize the design, functionality, and aesthetics of the final product including personas, user stories, feature association, and a priority-feasibility matrix to determine the initial website structure of the website that applied this structure. We iterated mockup designs by conducting online focus groups with women with a history of ACS. Participants provided feedback on preferences for the device they would use; website settings, icons, and language; timing of reminders to complete daily symptom diaries; and understanding of the action plan and visual displays of symptom feedback to share with their provider. Eleven women (18% black; mean age 62.1) with varied digital literacy (36.4% never used ZOOM) from suburban (63.6%) or rural (36.4%) settings were included from 3 online focus groups. Participants determined website settings, icon, and language; initial symptom survey format; and language in the action plan and final visual display of symptom feedback data, respectively. A final focus group with 5 clinicians (2 cardiologists/3 nurse practitioners) provided input for modifications to the content, features, and scientific rationale for design decisions prior to finalizing the product. By delivering the intervention in an online acceptable format, we can reach women from rural settings who otherwise may not have completed a structured educational program post-ACS.
Abstract 13576: Retinoic Acid Enhances Phenotypic Characteristics of Alternative Activation in Macrophages
Authors: Pinos Ivan , Amengual Jaume
Published: April 2022

Introduction:
Macrophages are key players in atherosclerosis, an inflammatory condition that leads to cardiovascular diseases. Classically-activated (M1) macrophages show a pro-inflammatory phenotype, whereas alternatively-activated (M2) are anti-inflammatory. The M1/M2 balance in atherosclerosis determines the fate of the lesions and strategies to increase M2-like macrophages entail promising candidates against atherosclerosis. We have previously shown that vitamin A delays atherosclerosis progression in mice, and others have proposed retinoic acid (RA), the transcriptionally active form of vitamin A, as a modulator of macrophage polarization.

Hypothesis:
RA modulates macrophage polarization by inducing M2-like responses.

Methods:
Bone marrow-derived macrophages (BMDM) from three wild type C57BL/6J mice were differentiated (M0) and stimulated with LPS/IFNγ (M1) or IL-4 (M2) for 24h, followed by 6h exposure to 1 μM RA or vehicle (DMSO). RNAseq and gene enrichment analysis was performed on differentially expressed genes. Autophagy flux and the lysosomal protein breakdown rate were analyzed.

Results:
RNAseq and differential gene expression analysis showed that RA induced changes in 1,485 genes in M2 macrophages, while 821 and 227 genes were significantly regulated in M0 and M1, respectively (FDR<0.05).
Arginase 1
, a well-known marker of M2 activation, was significantly upregulated by RA in M0 (FC=3.74; FDR=0.03) and M2 (FC=3.33; FDR=0.03). Autophagy and Lysosome pathways were significantly over-represented in M2 macrophages treated with RA (-log2 P=4.3 and 5.1, respectively). However, autophagy flux and protein breakdown rate were not affected by RA in M2.

Conclusions:
Transcriptomic data suggest that M0 and M1 macrophages are less responsive to RA in comparison to M2 macrophages. Even though RA seems to modulate the transcriptional machinery to induce the expression of autophagy genes, these changes did not alter autophagy flux or lysosomal degradation under our experimental conditions. Our data suggest that the responsiveness of M2 macrophages to RA might prompt phenotypic differences towards enhancing M2-like phenotype. Future experiments will explore the role of RA on other features of M2 polarization
Abstract 13580: DNA Methylation of Skeletal Muscle Tissue in Patients With Hypertension and Diabetes Undergoing Cardiopulmonary Bypass
Authors: Aghagoli Ghazal , Yano Naohiro , Del Re Andrew M , Zhang Zhiqi , Gheit Ahmad , Phillips Ronald , Feng Jun , Fedulov Alexey , Sellke Frank W
Published: April 2022

Introduction:
Epigenomic changes may affect the condition of patients before and after surgery. The epigenome-wide DNA methylation profiling of human skeletal muscle (SKM) specimens obtained from patients undergoing cardiac surgery utilizing cardiopulmonary bypass (CPB) was examined.

Hypothesis:
We hypothesized that regulatory changes in SKM that develop in patients with HTN and DM include epigenetic regulation and aimed to characterize the epigenome-wide signature of these changes, both at baseline and after cardiac surgery.

Methods:
SKM was obtained from the internal mammary artery bed before and after termination of cardiopulmonary bypass. Specimens of patients without hypertension or diabetes (control), those with hypertension alone (BP ≥ 130), those with hypertension combined with either controlled (HbA1C <=7) or poorly controlled (HbA1C > 7) diabetes were examined. SKM DNA methylation was profiled via Illumina MethylationEpic arrays and analyzed by principal component analysis, cluster analysis and analysis of variance followed by network and pathway analysis.

Results:
DNA methylation in samples from patients with hypertension and diabetes was significantly different in 5822 loci for controlled diabetes and in 7177 loci for uncontrolled diabetes; hypertension alone produced minimal effect. These loci produced a tightly interacting network with 560 hubs and 7055 edges. These loci were associated with genes involved in pathways of IL-1, IL-12, IL-18, TNFα; IFNγ and VEGF signaling, in NF-κB and Wnt pathways, apoptosis and DNA damage response. SKM at the end of CPB revealed 282 highly significant loci or 193,567 loci with lower significance and the magnitude of the effect not exceeding 10-20%.

Conclusions:
Preoperatively, patients with diabetes show substantial change in SKM DNA methylation epigenome wide. Compared to diabetes, hypertension did not as substantially influence the methylome in the SKM. During surgery multiple low-grade methylation changes occur that may mask the effects of the disease; moreover in a few loci more prominent changes occur that may be part of a compensatory/regulatory response to surgery utilizing CPB.
Abstract 13582: A Quality Improvement Project to Increase Primary Care Follow Up After Congestive Heart Failure Exacerbation in an Academic Medical Center Using a Quality and Safety Award
Authors: Monday Lea , Sebastian Joseph , Nguyen Paul , Yazdanpanah Omid , Solokowski Caleb , Chi Jane , BAZZY KAREEM
Published: April 2022

Introduction:
Readmission after Congestive heart failure (CHF) exacerbation may be reduced by early follow-up with primary care physicians (PCP). We present a resident-driven quality improvement (QI) initiative to increase early follow-up for Veterans after CHF exacerbation. Primary outcomes were percentage of PCP follow-up within 7-days and median time to follow-up. Secondary outcomes were percentage of patients attending a PCP visit within 7-days, 30-day readmission, and mortality.

Methods:
This pre-post quasi-experimental study evaluated concurrent QI interventions including a standardized discharge scheduling order, monthly education, and aggregated performance feedback for medical residents with an award to the team with the highest rate of PCP appointments scheduled within 7-days (Fig 1). Patient characteristics and outcomes for a 6-month historic period and 6-month intervention period were compared using test of proportions and Wilcoxon Rank-Sum test.

Results:
A total of 294 patients were discharged due to CHF exacerbation (161 in historic group and 133 in intervention group). Appointments scheduled within 7-days increased from 43% to 79% (p<0.001). Median time to follow-up decreased from 8 to 6 days (p<0.001). A control chart is shown in figure 2. Patients who completed a PCP appointment within 7-days increased from 16% to 41% (p<0.001). 30-day readmission and mortality were unchanged.

Conclusion:
A standardized discharge scheduling order, robust resident education, and a monthly patient safety and quality award resulted in a significant increase in the rate of primary care follow-up within 7-days of CHF exacerbation.
Abstract 13584: Outcomes and Associated Costs With Temporary Mechanical Circulatory Support Devices in Patients With Cardiogenic Shock
Authors: Malik Aroosa , BASU TANIMA , Shore Supriya
Published: April 2022

Objective:
Clinical outcomes and costs associated with different temporary mechanical circulatory support (tMCS) devices has not been previously described. We describe outcomes and costs among heart failure (HF) patients who received tMCS i.e. Impella, intra-aortic balloon pump (IABP) or extra-corporeal membrane oxygenator (ECMO).

Methods:
This was a retrospective study of a large administrative claims dataset between 01/01/10 and 12/31/19. We included patients with HF or cardiogenic shock who received tMCS i.e. Impella, IABP or ECMO in the absence of an acute myocardial infarction (AMI) or coronary revascularization. Outcomes studied included 30-day mortality, in-hospital stroke and bleeding. We used logistic regression techniques to evaluate association between tMCS device, outcomes and cost.

Results:
We included 2205 HF unique patients receiving tMCS in the study: 1503 (68%) with ischemic cardiomyopathy (ICM) and 702 (32%) with non-ischemic cardiomyopathy (NICM). Rate of 30-day mortality was higher with ECMO compared to IABP or Impella respectively (22% vs. 15% vs. 17%) with higher stroke (21% vs. 12% vs. 16%) and bleeding rates (42% vs. 25% vs. 33%). This association persisted with multivariable adjustment for all adverse events. ECMO has higher odds of all adverse events vs IABP. Impella has higher odds than IABP for bleeding only. Median standardized cost was highest with ECMO $210383.0 (IQR: $165,760-$239,373), followed by Impella $142,518 (IQR: $126,845-$179938) and IABP $132,059.7 (IQR: $113,794-$160,243.7). Overall, we noted a decrease in cost with ECMO and IABP device types during the study period per year (Figure1).

Conclusion:
In a cohort of HF patients without AMI or coronary revascularization, use of ECMO was associated with higher rates of 30-day mortality, in-hospital stroke and bleeding compared to IABP and Impella. Associated costs with tMCS use are rising with an increase in survival over time.
Abstract 13592: QRS 3D Voltage Time Integral (3D QRS Area) is a Predictor for Pacing Induced Cardiomyopathy
Authors: Lacy Sean , Parimi Nikhil , Morey Tucker , Mahmood Uzair , Harvey Chris , Sheldon Seth , Reddy Madhu , Noheria Amit
Published: April 2022

Introduction:
The instantaneous absolute 3D ECG voltage integrated over the duration of QRS (VTI
QRS-3D
), also measured as 3D QRS area, is a marker for left ventricular electrical dyssynchrony in patients with left bundle branch block.

Hypothesis:
We sought to investigate if VTI
QRS-3D
predicts pacing induced cardiomyopathy in patients with chronic (>3 months) right ventricular pacing (RVp).

Methods:
We retrospectively evaluated RVp ECGs from consecutive patients with pacing induced cardiomyopathy (left ventricular ejection fraction ≤50%) and compared to patients with normal ejection fraction (>50%). Patients were excluded if they did not have ECG and/or echocardiogram. 12-lead ECGs were converted to orthogonal X, Y, Z leads using Kors matrix. VTI
QRS-3D
was obtained by voltage-time-integral from root-mean-squared 3D ECG.

Results:
We analyzed 320 RVp patients (age 73 ± 14 years, 40% female), 206 with preserved ejection fraction (LVEF 60.4 ± 4.1%) and 114 with pacing induced cardiomyopathy (LVEF 29.2 ± 8.1%). Pacing induced cardiomyopathy was associated with a longer QRS duration, larger QRS voltage and larger VTI
QRS-3D
(Table). VTI
QRS-3D
≥90 μVs had 81% sensitivity to identify pacing induced cardiomyopathy (specificity 47%).

Conclusions:
In the setting of chronic right ventricle pacing, QRS 3D voltage time integral ≥90 μVs on ECG can be used as a screening tool to identify patients needing further evaluation for cardiomyopathy.
Abstract 13597: Poorer Outcomes Associated With More Invasive Lead Management Strategies for Abbott Riata® Leads in a Large, Multi-Center Retrospective Study
Authors: Mar Philip , Patel Hiren , Horbal Piotr , Tsai Christina , Bhakta Deepak , Kabra Rajesh , Longserre Sarah , Hussein Ahmed , Olshansky Brian , Dickey Sierra , Lakkireddy Dhanunjaya R , Gopinathannair Rakesh
Published: April 2022

Introduction:
Abbott Riata® (AR) leads are prone to conductor externalization but have similar annual failure rates compared to industry benchmarks. A recent multi-center study showed that lead extraction (LE), lead abandonment (LA), and generator change only (GC) have similar long-term outcomes for the recalled Sprint Fidelis® and AR leads when analyzed collectively. However, a study evaluating only AR lead management with these strategies has not been done. We sought to evaluate if outcomes are worse with more invasive strategies (LE and LA) vs. GC when managing AR leads.

Hypothesis:
To compare outcomes after LE, LA, and GC strategies for AR leads.

Methods:
This is a 5-center, retrospective study evaluating LE, LA and GC strategies for AR. The incidence of peri-procedural complications, 60-day extended or repeat hospitalization [ERHOSP], death within 60 days, subsequent lead malfunctions, and long-term mortality were compared amongst LE, LA, and GC strategies.

Results:
165 patients (65± 13 years, 68% male) were followed for a mean 33 ± 30 months following intervention. Outcomes are listed on Table 1. Total AR lead dwell time follow-up was 16633 months. A total of 3 AR lead malfunctions were noted during long-term follow-up. Inappropriate shocks were similar between LE 7.7% (1/13), LA 6.3% (1/16) and GC 11.0% (15/136); P=0.74.

Conclusions:
More invasive lead management (LE and LA) resulted in increased death within 60 days and ERHOSP after adjusting for long-term lead malfunction with GC. Long-term mortality was also more favorable in the GC group. AR leads should only be extracted or revised if they demonstrate evidence of lead malfunction when the device reaches end of life.
Abstract 13604: Patient Centered Prescription Using Optimization Algorithms for Statin Users
Authors: Liang Yue , Lenskaia Tatiana , Loth Matt , Pradhan Prajwal , Yew Pui Ying , Robinson Jennifer G , Adam Terrence , Chi Chih-lin
Published: April 2022

Introduction:
Clinical decision support (CDS) that does not optimize individual variability with best practice and treatment outcomes, cannot support patient-centered care. For example, a statin treatment CDS focused on cholesterol reduction without accounting for patient comorbidities, at risk lifestyle, or genetics, may well suggest a treatment that increases adverse effects, has a high cost, and has a low potential for improved outcome. We present a novel patient-centered decision support (PCDS) system for statin initiation that accounts for best practice and patient variation and ranks treatment options by their predicted ability to improve cardiac outcomes and reduce adverse effects for individual patients.

Method:
A total of 30 M de-identified claim records from 1.4 M adults receiving statin treatment over 1990-2020 are available in the OptumLabs® Data Warehouse and were used to train our counterfactual prediction algorithm. For a new patient, the PCDS system predicts LDL reduction, cardiac events, and other outcomes at 1 and 5 years, for every potential statin treatment. The PCDS then integrates doctor and patient preferences into a multi-objective optimization algorithm to generate a ranked list of treatment options.

Conclusion:
Our novel patient-centered decision support (PCDS) adds sophisticated AI modeling and optimization to account for evidenced-based best practice, patient variability, and adverse effect risk to produce a clear ranking of treatment options that can be re-ranked upon input of patient preferences and provider’s lifestyle, socioeconomics, culture, experience and environment factors. This PCDS approach leverages traditional CDS adjusted to individual preferences to aligned with the patient-centered care model.
Abstract 13617: Trends and Outcomes of Endocarditis in Patients Undergoing Hemodialysis in Contemporary US Population From 2016-18
Authors: malik senada , Aronow Wilbert S
Published: April 2022

Background:
With increasing valvular interventions, the incidence of endocarditis in patients on chronic dialysis is significantly increasing. Therefore, we aimed to investigate and compare the contemporary outcomes and trends of endocarditis in patients receiving dialysis.

Methods:
All hospitalizations with a primary diagnosis of endocarditis between 2016 and 2018 identified in the Nationwide Inpatient Sample were categorized into those with or without chronic dialysis. The primary outcomes were inpatient mortality. Survey techniques were used to do comparative analyses using Stata.

Results:
Of 53,950 endocarditis hospitalizations that met inclusion criteria, 6,075(11.26%) had endocarditis with chronic dialysis. In-hospital mortality in endocarditis patients with and without chronic dialysis was 18.8% vs. 7.7%. Hospitalizations for endocarditis with chronic dialysis were associated with higher prevalence of diabetes (16.7% vs. 9.8%), hypertension (27.7% vs. 21.2%), coagulopathy (28.7% vs. 19.3%), sepsis (59.3% vs. 43.7%), liver disease (17.2% vs. 11.4%), congestive heart failure (54.5% vs. 39.6%) and renal failure (88.8% vs. 24.0%) as compared with endocarditis without chronic dialysis, all p-values <0.05. Hospitalizations for endocarditis with chronic dialysis was seen less likely in patients with valvular disease (54.9% vs. 67.3%), solid tumor without metastasis (2.2% vs. 4.2%), and smoking (15.2% vs. 25.7%), all p-values <0.05. In a multivariable logistic regression model, the patients with chronic dialysis were two times likely to die from endocarditis OR 1.97 (1.66-2.34; p-value <0.001). Older age, liver disease, and higher elixhauser score were the independent predictors of in-hospital mortality in patients with chronic dialysis who had endocarditis.

Conclusions:
The prevalence of chronic dialysis has been increasing in patients with endocarditis and it contributes to significant complications including sepsis and mortality.
Abstract 13618: Novel Fumarate Prodrug Rescues Cardiomyopathy and Motor Function in Friedreich’s Ataxia
Authors: Montgomery Claire B , Flores Veronica , Sims Landon , Thai Phung N , Chiamvimonvat Nipavan , Cortopassi Gino , Dedkova Elena N
Published: April 2022

Background:
Friedreich ataxia (FA) is a monogenic recessive ataxia caused by reduction of a single mitochondrial protein, frataxin (FXN), for which there is no approved therapy. Although the name of FA refers to the neurodegenerative ataxia, the lethal event is cardiomyopathy, caused by deficient FXN expression in the heart. Through a drug discovery screening program, we identified that bioactive fumarates are protective in FA cell models. We have subsequently developed a novel monomethyl fumarate precursor which has a higher retention time in the gut and also releases nicotinamide
(
NAD
+
).

Hypothesis:
To test the hypothesis that novel NAD
+
and fumarate precursor IMF provides more efficient protection against development of lethal cardiomyopathy in the inducible mouse model of FA (FXNKD) compared to a known fumarate precursor dimethyl fumarate (DMF, also known as Tecfidera).

Methods:
To suppress FXN expression, FXNKD mice were fed doxycycline chow and cardiac function was examined by
in-vivo
echocardiography. Aconitase activity, used as a surrogate measure of frataxin’s iron-sulfur biogenesis function, complex I and II activities, NAD
+
/NADH levels were measured by biochemical assays.

Results:
FXNKD and CTL mice were given vehicle, DMF or IMF daily for 8 weeks at concentrations that match the equimolar amount of monomethyl fumarate (MMF) released by the drugs. After 4 weeks of doxycycline treatment, FXNKD mice developed significant balance and locomotor deficits as assessed by the rotarod, 16 mm balance beam and open field tests. All neurobehavior parameters were improved after 8 weeks of treatment with IMF but not with DMF. Echocardiography revealed a significant increase in left ventricular wall thickness, and a decrease in LV internal diameter, stroke volume, and cardiac output, hallmarks of clinical cardiomyopathy in FA patients. IMF but not DMF prevented a decline in cardiac function in FXNKD mice. FXNKD mice treated with IMF showed increase in FXN expression levels, NAD
+
/NADH, aconitase and complex I and II activities.

Conclusions:
Because cardiomyopathy is the usual lethal event in FA, we suggest that nicotinamidated monomethyl fumarate is more potent drug compared to DMF and could improve the quality of life in FA affected individuals.
Abstract 13622: Current of Injury is an Indicator of Lead Depth and Acute Perforation During Left Bundle Branch Pacing Lead Implantation
Authors: Chen Xueying , Shali Shalaimaiti , Su Yangang
Published: April 2022

Background:
Left bundle branch(LBB)pacing has emerged as a favorable option that utilizes cardiac conduction system. Monitoring lead depth in the septum is crucial to reach the LBB area and to avoid lead perforation but lacks informative approach. We aimed to assess the hypothesis that current of injury (COI) is a useful tool in guiding depth of lead and forecasting perforation.

Methods:
Consecutive patients who received LBB pacing with distinct LBB potential were enrolled from January 2018 to December 2020. Unipolar intracardiac electrogram was recorded from both tip and ring electrode at the time of lead fixation. The maximum amplitude of ST-segment elevation from baseline was defined as COI.

Results:
LBB pacing lead implantation was attempted for 1223 times in 512 patients (age 66.25 ± 15.20 years, 310 male). Discrete COI (ST-segment elevation more than 25% of intrinsic R wave amplitude) was present in 92.70% of the cases (1134/1223) on tip electrode while only in 68.1% of the cases (833/1223) on ring electrode. COI tip/COI ring was correlated with the lead depth determined by sheath angiography (Spearman’s Correlation Coefficient=-0.624,
p
=0.000). Acute lead perforation has occurred in 11 cases when COI was either absent or very low on tip electrode. Among them, only eight cases, noted as microperforation, displayed significant COI on ring electrode, and COI tip/COI ring was extremely low (0.063, 0.035-0.123). The COI tip/COI ring<1 is associated to lead perforation (OR: 30.24, 6.47 -141.3, p=0.000). Sensitivity, specificity, and positive and negative predictive values of COI tip/ring<1 as an early marker for lead perforation were 81.8%, 87.1%, 54.2% and 99.8%, respectively.

Conclusions:
In conclusion, COI tip/ring could help to understand the depth of lead inside ventricular septum. Lack of COI on tip electrode or a very low COI tip/COI ring may signal lead perforation.