bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11700: Hemodynamic Impact of Severe Pulmonary Regurgitation in Patients With Right Ventricular Hypertension Secondary to Peripheral Pulmonary Arterial Stenosis
Authors: Hagel Jonathon A , Ruberto Anthony , Porras Diego , Maschietto Nicola
Published: March 2022

Introduction:
Severe pulmonary regurgitation (PR) is a common sequela of surgery for dysfunctional right ventricular outflow tract (RVOT). Peripheral pulmonary arterial stenosis (PPS) is frequently associated with conotruncal anomalies like Tetralogy of Fallot. Whether severe PR, which increases the right ventricular stroke volume, worsens right ventricular hypertension (RVHTN) in patients with PPS has not been previously investigated.

Hypothesis:
In patients with RVH secondary to PPS, the abolishment of severe PR ameliorates the degree of RVH.

Methods:
Retrospective longitudinal study of patients with PPS and severe PR, who underwent transcatheter pulmonary valve replacement (TPVR) at Boston Children’s Hospital between 01/2016 and 12/2019. Patients were included if they met all 3 of the following criteria: (1) PPS, (2) RVHTN immediately before TPVR (defined as an RV to Ao systolic pressure ratio [RV/AO] of at least 0.5 after interventions on the RVOT/PPS and before TPVR), and (3) severe PR. Patients with missing data were excluded. Hemodynamic data were collected at baseline, before TPVR (following the interventions for PPS and on the RVOT), and after TPVR. Variables were analyzed using a repeated-measure non-parametric ANOVA (Friedman test). A post-hoc analysis with Dunn-Bonferroni adjustment was performed.

Results:
In the study period, 17 patients (median age 14.6 years, IQR 10.1-19.7) met the inclusion criteria and had available hemodynamic data. Right ventricle systolic pressure, RVOT gradient, and RV/AO changed significantly overtime (all p<0.001). While there was no significant difference in RVOT gradient before and after TPVR, re-establishment of valve competence did result in a further significant drop in RV pressure (Table 1).

Conclusion:
In patients with RVHTN secondary to PPS and severe PR, reestablishment of pulmonary valve competence significantly decreases the degree of RV hypertension compared to RVOT/PPS interventions alone.
Abstract 11701: Ultrasound Acceleration Does Not Provide Detectable Benefit During Catheter-Directed Thrombolysis for Massive or Submassive Pulmonary Embolism: A Meta-Analysis of the Available Evidence
Authors: Combiths Adam M , Gao Feng , Alam Mahboob
Published: March 2022

Introduction:
Compared with systemic thrombolysis, catheter-directed thrombolysis (CDT) for acute pulmonary embolism (PE) reduces the risk of mortality and major bleeding due to lower thrombolytic doses. The only FDA-approved device for CDT is a more expensive ultrasound-accelerated CDT (USAT) device, which uses high frequency ultrasound waves to disrupt the fibrin mesh of the thrombus. No trials comparing CDT vs USAT exist. We conducted a meta-analysis of all published studies that employed CDT and/or USAT for acute PE, stratified by PE severity.

Hypothesis:
Ultrasound acceleration will improve mortality, bleeding risk, and right heart strain in acute PE over standard CDT.

Methods:
We performed a retrospective non-time-limited literature search of PubMed for all studies of either catheter-directed thrombolysis technique. Outcome measures (30-day mortality, major bleeding, RV/LV ratio, pulmonary artery systolic pressure) were extracted. Meta-analyses were performed using RevMan Review Manager 5.3 (Cochrane Collaboration). Random Effects Model was used to calculate proportion, mean difference, and Chi-square with 95% confidence intervals.

Results:
Of 1260 patients in the 34 identified studies, 311 had massive PE, and 928 underwent USAT. There was no difference between CDT and USAT in 30-day mortality in massive PE (27% [7, 48] vs 30% [-2, 62], Chi2=0.02, p=0.90, I2=40%) or submassive PE (5% [-5, 15] vs 3% [0, 7], Chi2=0.16, p=0.69, I2=0%), in major bleeding in massive PE (21% [0, 43] vs 16% [2, 31], Chi2=0.15, p=0.70, I2=58%), in pulmonary artery systolic pressure in massive PE (md 25.73 [16.06, 35.40] vs 19.75 [5.38, 34.12], Chi2=0.46, p=0.50, I2=89%) or submassive PE (15.71 [10.31, 21.89] vs 15.62 [9.77, 21.47] Chi2=0.01, p=0.91, I2=85%).

Conclusions:
Both techniques are efficacious in improving mortality, bleeding, and right heart strain. However, few studies report outcomes for standard CDT, and between-study heterogeneity is high. Differences in 30-day mortality, major bleeding events, and markers of right heart strain were not detected between techniques in our met-analysis. Practitioners are left without evidence of benefit for ultrasound acceleration, pending the results of the ongoing randomized-controlled trial

.
Abstract 11703: In-Patient Heart Failure Education Program Associated With Improvement in Patient Reported Knowledge and Decrease in Readmission Rate
Authors: Sesay Isata , Ruppert Linda , Hamad Eman A
Published: March 2022

Background:
Heart failure (HF) is a progressive syndrome characterized by high mortality, lower quality of life and frequent hospitalizations. A major component of the economic and societal burden imposed by HF remains recurrent hospitalizations, with 30-days readmission rates of 27% nationally. We conducted a quality improvement project at our hospital with the aim to evaluate the impact of a structured nurse-led heart failure education program on patient’s heart failure disease management knowledge, discharge follow-up, and 30-days hospital readmission.

Method:
Our cohorts included adult patients admitted with Acute Decompensated Heart Failure and successfully completed a structured heart failure education based on the American Heart Association Heart Failure Education guide. Patient also completed a pre-and-posttest to assess their level of understanding of heart disease management which included self-monitoring behaviors.

Results:
Between March and June 2021, 41 patients participated in the heart failure education session. The mean pre-test and post-test score was 58% versus 74%, with an average improvement of 16% in participants knowledge about heart failure disease management and self-care. Overwhelming majority of the patients (85%) were satisfied with their heart failure education. Eighty-Five percent of the participants had hospital follow-up appointment scheduled within seven days and 76% of them were compliant with follow-up. These patients had a lower 30-day readmission rate at 15% compared to our centers current rate at 21%.

Conclusion:
This retrospective, single-center observation study found that a structured inpatient heart failure educational program was associated with patients reported improvement in HF disease management knowledge. We observed a reduction in heart failure related hospital readmission compared to our center’s average and the national average. There was also an improvement in 7-day discharge follow up.
Abstract 11704: NF-κβ Signaling Regulates Vasopressin Receptor 2 Promoter Activity
Authors: Dingwell Luke S , Afroze Talat , Momen Abdul , Zhou Annie , Siraj M. Ahsan , Jafrani Areeb R , Husain Mansoor
Published: March 2022

Background:
Arginine vasopressin, through vasopressin receptor 2 (AVP-V2R), regulates water reabsorption via aquaporin-2 and sodium reabsorption via several mechanisms. We recently implicated V2R, and its transcriptional downregulation, in a model of B-cell deficiency with increased sodium- and water-excretion and reduced blood pressure (BP). Here, we identify mechanisms underlying the immunoregulation of V2R transcription and evaluate the importance of V2R in BP regulation.

Methods & Results:
Using an
Avpr2
promoter-luciferase reporter in an immortalized mouse inner medullary collecting duct cell line [mIMCD-3], we found that IL-6 (100ng/mL), a stimulator of NF-κβ signaling, increased promoter-reporter activity (10.4±3.2
vs
4.0±0.5 RLU; N=2-3/group); while PDTC (60μM), an inhibitor of NF-κβ signaling, reduced promoter-reporter activity (2.2
vs
4.0±0.5 RLU; N=1-3/group). Importantly, single point mutations in two putative NF-κβ binding sites in the proximal
Avpr2
promoter also reduced promoter activity (2.3±0.6
vs
4.0±0.5 RLU; N=2-3/group), and blocked the stimulatory effect of IL-6 (2.4
vs
2.3±0.6 RLU; N=1-2/group). An anti-IL-6 receptor antibody (10μg/mL
vs
isotype, 10μg/mL) also abolished the stimulatory effect of IL-6 on promoter activity (3.2
vs
9.1 RLU; N=1/group). To determine the role of V2R in BP regulation, wild-type C57BL/6J mice (male and female; aged 10-wk) were randomized to (i) Tolvaptan (TOL), a selective V2R-antagonist or (ii) DMSO/glycerol control (50/50) via osmotic mini-pump (0.0375mg/d). Invasive hemodynamics 12-d post-implant revealed reduced mean arterial pressure (MAP) in TOL-treated mice (76±3
vs
86±3 mmHg; N=4-5/group; P<0.05), while metabolic cage studies 8-11-d post-implant showed higher 24-h urine volume/body weight (UV/BW; 0.07±0.00
vs
0.05±0.00 mL/g; N=4-5/group; P<0.05) and 24-h sodium excretion/BW (0.25±0.01
vs
0.17±0.01 mg/d/g; N=4-5/group; P<0.01). Correlation analyses revealed inverse relationships between MAP and 24-h UV/BW (r=-0.65; N=9 pairs; P<0.05) and 24-h sodium excretion/BW (r=-0.64; N=9 pairs; P<0.05).

Conclusion:
These studies suggest that the V2R promoter is responsive to NF-κβ signaling, and that V2R serves a role in BP homeostasis through sodium- and water-handling.
Abstract 11721: FOXK1 is an Essential Transcriptional and Epigenetic Regulator of Cardiovascular Development
Authors: Sierra-Pagan Javier , Dsouza Nikita , Larson Thijs A , Das Satyabrata , Stan Patricia , Gong Wuming , Garry Mary G , Garry Daniel J
Published: March 2022

Background:
Congenital heart disease (CHD) is the most common genetic birth defect and has considerable morbidity and mortality. Therefore, it is essential to define the mechanisms governing the specification and differentiation of mesodermal and cardiac progenitors to develop targeted therapies for CHD. FOXK1 is a forkhead/winged helix transcription factor known to regulate cell cycle kinetics, myogenic stem cell proliferation and tumorigenesis. During development, FOXK1 expression is restricted to mesodermal progenitors, somites and the heart. The role for FOXK1 in the developing heart is unknown and warrants investigation. In the present study, we describe a novel role for FOXK1 as an essential regulator of cardiovascular development.

Approach and Results:
We used a mouse embryoid body (EB) system to differentiate WT and
Foxk1
null ESCs into mesodermal and cardiac progenitor cells. Flow cytometry analysis for FLK1+PDGFRa+ showed that in the absence of FOXK1, the cardiac lineage was significantly affected. Bulk RNAseq analysis of D3 and D5 EBs showed a significant induction of the cardiac molecular program in WT EBs compared to the
Foxk1
null EBs. Since forkhead transcription factors have been shown to be important epigenetic regulators (i.e. pioneer factors), we performed ATACseq of D3 and D5 EBs, which showed that the chromatin landscape nearby known important regulators of cardiogenesis (Isl1, Gata4, Hand1, Hand2, etc.) was significantly relaxed in WT EBs compared to
Foxk1
null EBs. Furthermore, we demonstrated that in the absence of
Foxk1
, cardiac differentiation was markedly impaired by assaying for cTnT expression and cardiac contractility which was essentially absent in
Foxk1
null EBs compared to WT EBs at D10 of differentiation. Additionally, using transcriptional, Co-IP and pulldown assays we demonstrated that FOXK1 is an important regulator of Notch and Wnt/β-catenin signaling pathways during cardiogenesis. These results were further supported as the
Foxk1
null embryo was lethal at E9.5 and had perturbed heart development.

Conclusions:
These results identify FOXK1 as an essential transcriptional and epigenetic regulator of cardiovascular development using EB assays and gene disruption technologies.
Abstract 11722: Assessing Disparity of Performance Measure by Door-to-Balloon Time Between Rural and Urban Area for Management of Patients with ST-Segment Elevation Myocardial Infarction -Insights from the Nationwide Japan Acute Myocardial Infarction Registry-
Authors: Fukui Kento , Takahashi Jun , Hao Kiyotaka , Honda Satoshi , Kojima Sunao , Takegami Misa , Sakata Yasuhiko , Itoh Tomonori , Watanabe Tetsu , Takayama Morimasa , Sumiyoshi Tetsuya , Kimura Kazuo , Yasuda Satoshi ,   JAMIR Investigators
Published: March 2022

Background:
Door to balloon time (D2B) ≤90 minutes is a key indicator of quality of care for ST-segment elevation myocardial infarction (STEMI). The development of standardized management for STEMI may narrow the performance gap between rural and urban hospitals. However, there are few studies to explore the disparity of D2B and outcomes between rural and urban areas.

Methods and Results:
The Japan Acute Myocardial Infarction Registry (JAMIR) is a nationwide, real-world registry study. We retrospectively analyzed 17,938 STEMI patients (68±13 years, female 22.4%) treated with percutaneous coronary intervention, who were divided into the following two groups according to population density of 1147 persons/km
2
; patients hospitalized in rural area and those in urban area. Overall, the median D2B was 72 mins and 73% achieved the target D2B ≤90 mins. Patients with D2B ≤90 mins had a lower in-hospital mortality compared with those with D2B >90 mins (4.7% vs. 8,4%, P<0.001). Rural patients were characterized by higher age, more accumulation of coronary risk factors and a higher prevalence of Killip class ≥2 at presentation compared with urban patients. The median D2B was longer (70 mins vs. 62 mins, P<0.001) and achievement rate for D2B ≤90 mins was lower (70% vs. 75%, P<0.001) in rural group than urban group (
Figure A
). In-hospital mortality tended to be higher in rural group (6.1% vs. 5.5%, P=0.06), whereas the benefit in shortening of D2B was noted equally in both groups (
Figure B
).

Conclusions:
The real-world nationwide study of JAMIR demonstrated that shortening of D2B time was significantly associated with survival benefit of STEMI in both rural and urban area.
Abstract 11723: Depression and Obesity Are Associated with Chest Pain in Patients with Non-Obstructive Coronary Artery Disease
Authors: Vatsa Nishant , Mehta Puja K , Kimble Laura P , Higgins Melinda , Quyyumi Arshed A
Published: March 2022

Introduction:
Chest pain in patients with non-obstructive coronary artery disease (NO-CAD) is a major clinical problem impacting the quality of life and can present a therapeutic challenge for providers. The objective of this study was to identify clinical factors associated with chest pain frequency in NO-CAD patients. Mainly, we investigated the hypothesis that increased body mass index (BMI) and depression are associated with increased chest pain frequency in NO-CAD patients.

Methods:
We identified a sample of 439 patients with NO-CAD (mean age 55.3 years, 50% women, 72% white) in the Emory Cardiovascular Biobank, a database of patients who underwent coronary angiography for suspected myocardial ischemia. Sociodemographic variables, clinical risk factors like BMI, and Patient Health Questionnaire 9 (PHQ9) results - a depression screening tool - were collected. We measured chest pain frequency through a questionnaire that asked patients how many times they had chest pain, chest tightness, or angina over the preceding four weeks. Within the sample, 180 patients (41%) reported no chest pain, chest tightness, or angina, and 259 patients (69%) reported one or more instances of chest pain, chest tightness, or angina in the preceding four weeks. We compared these two groups using t-test, Mann-Whitney U test, and multivariate logistic regression analyses.

Results:
The sample mean BMI was 30.6 ± 6.6 kg/m
2
. The median PHQ9 score was 3.0, with scores ranging from 0 to 27 and 34% having minimal to major depressive symptoms. Compared to those with no chest pain, patients with chest pain had higher BMI (31.5 ± 7.1 vs 29.4 ± 5.6 kg/m
2
, p=0.001) and higher PHQ9 scores (median [interquartile range]: 4 [1,8] vs 1 [0,3], p<0.001). Furthermore, higher BMI and PHQ9 scores were associated with higher odds of chest pain (odds ratio [95% confidence interval]: 1.041 [1.004-1.079] and 1.104 [1.044-1.168], respectively).

Conclusions:
In patients with NO-CAD, higher BMI and PHQ9 scores were associated with higher chest pain frequency. Thus, weight and depression optimization could reduce symptoms and improve quality of life in NO-CAD patients; however, this needs further study.
Abstract 11732: Hybrid Convergent Ablation of Atrial Fibrillation With Left Atrial Appendage Exclusion Improves Blood Pressure Control
Authors: Malyshev Yury , Tsutsumi Ayaka , Greenberg Yisachar , Yang Felix
Published: March 2022

Introduction:
Hybrid convergent ablation (HCA) of atrial fibrillation (AF) and left atrial appendage exclusion (LAAE) have evolved as alternative strategies to conventional rhythm control and stroke prevention, respectively. Recent data suggests that HCA and LAAE can substantially impact arrhythmia burden and hemodynamic profile.

Hypothesis:
We assessed the hypothesis that HCA with epicardial LAAE may reduce blood pressure (BP) and the number of medications required for its control.

Methods:
This is a retrospective study of 100 patients who underwent HCA with epicardial LAAE using AtriClip. Clinical outcomes were measured at 3 months and 1 year. Primary outcome was reduction in the number of BP medications compared to baseline. Secondary outcomes included dose reduction, composite of dose and number of medication reduction compared to baseline; changes in diastolic (DBP) and systolic BP (SBP).

Results:
At baseline, the mean number of BP reducing medications was 2.17 ± 1.3, SBP 130 ± 16.9 mmHg and DBP 80 ± 10.3 mmHg. The number of medications had decreased significantly both at 3 months (1.7 ± 1, p=0.005) and at 1 year (1.75 ± 1.1, p=0.015). 43% and 44% of patients had decreased the number of medications at 3 months and 1 year, respectively; 78% and 73% of patients had decreased the number and/or dose of medications compared to baseline at 3 months and 1 year, respectively. DBP was also significantly lower compared to baseline both at 3 months (75 ± 9.5 mmHg, p=0.00065) and 1 year (75 ± 10.6 mmHg, p=0.004). There was a trend towards lower SBP at 3 months (127 ± 16 mmHg, p=0.14) and 1 year (127 ± 15.8 mmHg, p=0.15).

Conclusion:
In conclusion, HCA with epicardial LAAE significantly decreases the number of BP medications required to control BP and significantly reduces DBP.
Abstract 11742: Knowledge on Anticoagulation Use in Atrial Fibrillation With Left Atrial Appendage Thrombus Among Medicine Residents
Authors: Brankovic Milos , Markovic Nebojsa , Nikolina Markovic , Kim Hyoeun , Aziz Emad
Published: March 2022

Introduction:
Left atrial appendage (LAA) thrombus increases thromboembolic risk in patients with atrial fibrillation (AF). Importantly, 40% of LAA thrombus patients will have an inadequate response to anticoagulation during follow-up. Of note, these patients are frequently followed by medicine residents in the clinic. Therefore, we aimed to explore residents' knowledge on anticoagulation use for the treatment of LAA thrombus.

Hypothesis:
Insufficient knowledge on anticoagulation for the treatment of LAA thrombus could contribute to inadequate treatment response during patients' follow-up.

Methods:
All medicine residents (n=96) at Rutgers University New Jersey Medical School were emailed a 26-question survey on the indication, dosing, pharmacokinetics and clinical experience using direct oral anticoagulants (DOACs) and vitamin-K-antagonists (VKA) in AF patients with LAA thrombus.

Results:
Of 62 responders, 42 (68%) have been prescribing DOACs in the clinic with apixaban being most commonly prescribed. Thirty-seven (61%) indicated DOACs as the first-line agents for LAA thrombus whereas 24 (39%) chose VKA. Nineteen (33%) responders indicated apixaban dosing correctly, and 51 (84%) indicated appropriately relation of apixaban with meals. If follow-up imaging reconfirmed LAA thrombus, 54 (89%) would switch to VKA whereas 7 (11%) would use other DOACs. Nineteen (32%) responders indicated rivaroxaban dosing correctly and only 10 (16%) indicated appropriately how to administer rivaroxaban with meals. If follow-up imaging reconfirmed LAA thrombus, 43 (71%) would switch to VKA whereas 18 (29%) would use other DOACs. Forty-one (72%) responders indicated dabigatran dosing correctly and 36 (58%) indicated no relation to food intake. If follow-up imaging reconfirmed LAA thrombus, 40 (65%) responders would switch to VKA whereas 22 (35%) would use other DOACs. For VKA, 51 (88%) indicated therapeutic INR range of 2-3 and 7 (12%) chose 2.5-3.5. If follow-up imaging reconfirmed LAA thrombus, 38 (61%) would increase INR goal whereas 24 (39%) would switch to DOACs.

Conclusions:
This survey identified knowledge gaps in dosing and pharmacokinetics of DOACs among medicine residents despite being more likely to prescribe DOACs over VKA to treat LAA thrombus.
Abstract 11749: Rates of Adverse Cardiovascular Outcomes in Patients With Peripheral Arterial Disease Did Not Vary by Neighborhood Deprivation Estimates
Authors: Nasser Mohamed Farhan , Jabri Ahmad , Thornton Daryl , Tarabichi Yasir , Gandhi Sanjay
Published: March 2022

Introduction:
Socioeconomic factors including neighborhoods with limited resources have a negative impact on cardiovascular outcomes in peripheral arterial disease (PAD) patients. An area deprivation index (ADI) quantifies a region’s socioeconomic conditions, which have been linked to health outcomes.

Hypothesis:
The patients with PAD living in disadvantaged neighborhoods as identified with higher ADI, will have higher co-morbidities and lower access to treatment, resulting in higher incidence of ST-elevation myocardial infarction (STEMI).

Methods:
Using electronic medical records, we identified patients with PAD (n=6331), using ICD 10 code of I 70 and I 73, with encounter from January 1, 2019 to June 2, 2021. Patients were stratified into four different groups by ADI. Baseline characteristics, comorbidities and medications were recorded for all patients. Using Wilcoxon Rank Sum Test and Pearson Chi Square tests, descriptive statistics are presented for baseline characteristics and comorbidities in table 1.

Results:
Patients with PAD with the highest ADI (n=1582), were younger (64 ±12), more likely to be African American (59.5%) and current smokers (41.4%) (p<0.001). There were significant differences in co-morbidities across the four groups of different ADIs (p<0.001), with hypertension (83.9% vs 69.6%), CHF (25.3% vs. 17.7%) and diabetes mellitus (15.1% vs.10.4%) being more common in the group with the highest ADI, compared to the group with the lowest ADI. These patients with the highest ADI, were also more likely to be prescribed aspirin, any antiplatelet, a statin or an ACE inhibitor (p< 0.001), suggesting appropriate access to medical therapy. However, the incidence of STEMI was not statistically significant between the groups (p=0.377).

Conclusions:
PAD patients living in neighborhoods with higher ADI have higher co-morbidities as compared to those in areas with lower ADI. The incidence of STEMI is low in all groups independent of ADI
Abstract 11750: Use of a Heart Failure Symptom Monitoring Tool With Individualized Visualizations to Report Longitudinal Patient-Reported Outcome Data
Authors: Mangal Sabrina , Reading Turchioe Meghan , Park Leslie , Myers Annie , Goyal Parag , Axsom Kelly , Masterson Creber Ruth M
Published: March 2022

Objective:
Evaluate feasibility of using a visualized symptom monitoring tool for patients with heart failure (HF) in a large academic medical center using mixed methods.

Introduction:
Patients with HF are frequently hospitalized with symptoms such as shortness of breath, fatigue, and swelling, and commonly report persistent symptoms one week after discharge. Many of these hospitalizations are preventable, emphasizing the need for improved methods for symptom monitoring and management.

Methods:
Quantitative summaries of ten symptoms were measured with the Patient-Reported Outcomes Measurement Information System-29 among patients with HF at baseline, 2, 4, 6, and 8 weeks with automated email follow-up. Symptom summary reports with visualizations previously developed using user-centered design were displayed at each time point to and showed changes in symptoms over time. Qualitative exit interviews were conducted with patients and healthcare professionals and were coded using directed content analysis.

Results:
65 participants completed all baseline surveys, and over half (n = 35, 54%) completed at least one follow-up survey (recruitment and follow-up ongoing). Based on mean PROMIS T-scores with a population mean of 50.0, participants reported highest symptom burden for: physical function (36.9 ± 9.0), fatigue (56.9 ± 12.0), and anxiety (55.4 ± 10.0). Interviews with patients (n = 18) and healthcare professionals (n = 5) highlighted that the tool was helpful for understanding health status and prompting communication, which might depend on patient agency. Suggestions for improvement included offering paper copies of symptom reports and follow-up phone calls (Table).

Conclusions:
Participants found the tool useful for understanding symptoms and prompting communication with the healthcare team. Future work should consider providing actionable symptom summaries to support patient agency and providing multiple options for format and follow-up.
Abstract 11752: Pitavastatin Treatment Ameliorates HIV-Nef Containing Extracellular Vesicle-Mediated Cardiomyocyte Dysfunction
Authors: Chelvanambi Sarvesh , Decano Julius , Kuraoka Shiori , Aikawa Elena , Singh Sasha A , Aikawa Masanori
Published: March 2022

Rationale:
The prevalence of cardiovascular diseases such as heart failure and left ventricular diastolic dysfunction remains high in People Living With HIV (PLWH) even with the advent of modern anti-retroviral therapy (ART). Sustained plasma persistence of the pro-inflammatory HIV protein Nef within extracellular vesicles (EV) of ART-treated patients may contribute to continued disease progression. We hypothesized that HIV-Nef induces cardiomyocyte dysfunction by elevating Reactive Oxygen Species (ROS) production which then increases apoptosis and senescence in cardiomyocytes.

Results:
Network analysis using
Metacore
of cytosolic and nuclear proteomics of human cardiomyocytes stimulated with HIV-Nef EV demonstrated changes in metabolic processes, DNA damage, oxidative stress and cytoskeletal remodeling. HIV-Nef EV promotes cardiomyocyte cellular dysfunction as evidenced by increased ROS production, DNA damage, apoptosis and premature senescence in both AC-16 cardiomyocyte cell line (n=5, p<0.001) and iPSC-derived cardiomyocytes (n=4, p<0.01). HIV-Nef EV stimulation induced cardiomyocyte metabolic switch by increasing consumption of anaerobic substrate (Lactic Acid) and decreasing consumption of TCA substrate (Citric Acid). [AE1] Network-science powered pathway analysis of HIV-Nef EV stimulated cardiomyocytes identified a key hub in Rac1-GTPase mediated pathways. Proteomic analysis of HIV-Nef transfected HEK293T cells indicated pitavastatin treatment altered Rac1 trafficking to inhibit interaction with HIV-Nef, suggesting a potential protective mechanism. Subsequently, cardiomyocyte dysfunction was abrogated by clinically relevant doses of pitavastatin (10-100nM ,n=4, p<0.01). Addition of HIV-Nef EV supernatant to AC-16 cardiomyocytes but not to those treated with pitavastatin increased chemotaxis of primary human macrophages (n=4, p<0.05).

Conclusion:
Pitavastatin treatment may prevent Nef EV-mediated cardiac dysfunction and inflammation in HIV patients. [AE1]I suggest including numbers of technical or biological replicates and p values when possible.
Abstract 11758: Prevention of Radiation-Induced Coronary Microvascular Leakage by the Restoration of an Endothelial Tight-Junction Protein
Authors: Nepali Sarmila , Xu Shirley , Sonkawade Swati D , Sharma Umesh C , Pokharel Saraswati
Published: March 2022

Introduction:
In cancer survivors exposed to ionizing radiation (IR) exposure to the chest and heart, coronary endothelial injury and disruption of vascular barrier integrity is noted. The mechanisms driving the IR-induced leakiness of the coronary microvasculature are not known. There is no therapy to prevent such injury.

Hypothesis:
IR exposure downregulates a tight junction protein claudin-1 (cldn1), which can lead to altered endothelial barrier integrity. Ac-SDKP, an endogenous peptide, prevents cldn1 loss and preserves coronary vascular barrier function.

Methods:
We tested the constitutive and physiological effects of cldn1 both
in vitro
and
in vivo
. Human coronary vascular endothelial cells (HMVECs) lacking cldn1 by siRNA silencing were used for loss-of-function studies. Newly developed vascular-specific (VE-cadherin promotor-linked) cldn1 overexpressing transgenic (TG) mice were used for cldn1 gain-of-function studies. Mice were exposed to 45Gy chest radiation in fractionated doses (3Gy/day). A subgroup of irradiated mice was treated with Ac-SDKP (3.2mg/kg/day) for 3-weeks. Evans blue dye was injected via tail-vein 30 mins before euthanasia and dye extravasation through coronary microvasculature was quantified. Cldn1 expression was examined by Western blot and
in vitro
cell permeability was examined by FITC-dextran permeability assays.

Results:
Cldn1 silencing with siRNA showed increased permeability in HMVECs (control, 1.0±0.01, siRNA, 1.3±0.01; p=0.0002). Cardiac irradiation significantly decreased myocardial cldn1 (control 1.0±0.27, IR 0.45±0.31; p=0.001). Consequently, there was a significant increase in myocardial Evans blue dye extravasation compared to controls (control 1.0±0.22, IR 1.3±0.23, p=0.039). Cldn1 overexpression mice had decreased dye extravasation compared to WT controls (WT 1.0±0.23, TG 0.38±0.27 p=0.002). Ac-SDKP restored cldn1 protein expression, and inhibited dye leakage in the myocardium after IR exposure (0.57±0.21, p=0.048 vs IR).

Conclusions:
Our study shows that IR exposure induces endothelial barrier disruption through a reduced expression of endothelial tight-junction protein, cldn1. Ac-SDKP prevents these effects, at least in part, by preventing loss of claudin-1.
Abstract 11760: Reducing Pulmonary Capillary Wedge Pressure During Exercise Does Not Improve Exercise Capacity in Heart Failure With Preserved Ejection Fraction
Authors: Macnamara James P , Sarma Satyam , Balmain Bryce , Hearon Christopher , Tomlinson Andrew R , Morris Margot , Livingston Sheryl A , Moran Raksa , Alcala Jessica N , Samels Mitchel , Payne Marcus , Boyd Tevrick , Babb Tony , Levine Benjamin D
Published: March 2022

Background:
Exercise intolerance is a defining characteristic of heart failure with preserved ejection fraction (HFpEF). A marked rise in pulmonary capillary wedge pressure (PCWP) during exertion is pathognomonic for HFpEF and is thought to be a key cause of exercise intolerance. If true, acutely lowering PCWP would improve exercise capacity. To test this hypothesis, we evaluated peak exercise capacity with and without nitroglycerin (NTG) to acutely lower PCWP during exercise in patients with HFpEF.

Methods:
In a preliminary analysis of a clinical trial, 15 patients with HFpEF (69±6 years, 60% female) underwent 2 upright, seated cycle exercise tests dosed with sublingual NTG or placebo control (CON), every 15 minutes in a single-blind, cross-over design. A right heart catheter was used to measure end-expiratory PCWP and cardiac output (Qc, direct Fick). Oxygen uptake was measured using breath-by-breath system. Measures were made at rest, 20W, and peak exercise.

Results:
PCWP increased from 6.0±2.4 to 33.7±7.4 mmHg from rest to peak exercise with placebo. With NTG, PCWP increased significantly less from 4.5±3.1 to 26.3±5.9 mmHg (drug x exercise p = 0.019). There was no change in peak VO
2
with NTG (CON: 1.25±0.36 vs NTG: 1.26±0.41 L/min, drug x exercise p = 0.986,
Figure
). Peak Qc was similar between conditions (Qc: CON 10.4±2.3 vs 10.8±3.2 L/min). During submaximal exercise, PCWP was lower with NTG with no difference in VO
2
(PCWP: CON 21.2±6.5 vs NTG 16.6±6.4 mm Hg, VO
2
CON:0.87±0.17 vs NTG 0.86±0.17 L/min) but with a lower stroke volume (NTG: 90±18 vs CON: 98±21 ml).

Conclusions:
Sublingual nitroglycerin effectively lowered PCWP during submaximal and maximal exercise. Despite this reduction in PCWP, peak VO
2
was not changed. These results suggest acutely lowering PCWP is insufficient to improve exercise capacity and raises the possibility that high PCWP during exercise is a secondary phenomenon rather than a primary cause of exercise intolerance in patients with HFpEF.
Abstract 11761: Association of Mitochondrial DNA Copy Number With Risk of Progression of Kidney Disease in the Chronic Renal Insufficiency Cohort (CRIC) Study
Authors: He William J , Kelly Tanika N , Li Changwei , Rao Varun S , Huang Zhijie , Hamm L L , He Jiang , Grams Morgan , Arking Dan E , Appel Lawrence J , Rebholz Casey M
Published: March 2022

Introduction:
Mitochondrial DNA copy number (mtDNA-CN) is a biomarker of mitochondrial function that has been associated with chronic kidney disease (CKD) and all-cause mortality in several community-based studies. However, there has been little research on mtDNA-CN and progression of CKD.

Hypothesis:
We hypothesized that higher mtDNA-CN will be associated with lower risk for CKD progression in a cohort of CKD patients.

Methods:
A total of 2,943 Chronic Renal Insufficiency Cohort (CRIC) study participants had mtDNA-CN calculated from probe intensities of mitochondrial single nucleotide polymorphisms (SNP) genotyped on the Illumina HumanOmni 1-Quad Array. To correct for batch effects, DNA quality, DNA quantity, and latent confounding factors, mtDNA-CN was regressed on 15 principal components generated from autosomal SNP probe intensity signals. mtDNA-CN residuals were then standardized to a mean of 0 and standard deviation of 1 and used in this analysis. CKD progression was defined as incident end-stage renal disease (ESRD) or halving of eGFR from baseline. Cox proportional hazards models were used to calculate hazard ratios for mtDNA-CN and risk of CKD progression.

Results and Conclusions:
Compared to patients in the lowest mtDNA-CN tertile, those in the middle tertile [HR=0.78, 95% CI: (0.68, 0.91)] and highest tertile [HR=0.78, 95% CI: (0.67, 0.91)] had a statistically significantly lower risk for CKD progression after adjustment for established risk factors (Table). Similar results were seen in race- and sex-stratified analyses (Table). These findings suggest that mtDNA-CN may have potential clinical utility in improving CKD risk classification. Furthermore, mitochondrial dysfunction has been hypothesized to contribute to renal disease through podocyte injury, tubular epithelial cell damage, and endothelial dysfunction. Future research on the mechanisms underlying mtDNA-CN and CKD progression may lead to novel strategies for CKD management.
Abstract 11762: The Proximity of the Stomach to the Inferior Wall of the Heart: Implications for Non-Invasive Radio-Ablation of Ventricular Tachycardia
Authors: Wu Bryan , Vanam Sai , Atwood Todd , Bruggeman Andrew , Moore Kevin , McVeigh Elliot , Han Frederick , Hsu Jonathan C , Hoffmayer Kurt S , Raissi Farshad , Birgersdotter-green Ulrika , KARUNAMUNI JENNIFER , Stark Paul , Feld Gregory K , Mundt Arno , Krummen David , Ho Gordon
Published: March 2022

Introduction:
Stereotactic ablative radiotherapy is a promising therapy for ventricular tachycardia (VT), but the formation of gastro-pericardial fistula is a serious complication associated with this procedure. The proximity of the stomach to the heart has not been well characterized.

Hypothesis:
We hypothesized that the stomach is located in close proximity (<1cm) to the inferior cardiac wall.

Methods:
Patients who underwent 4D cardiac computed tomography (4DCT) prior to a catheter ablation procedure for atrial or ventricular arrhythmias at 2 medical centers were studied retrospectively. 4DCT was acquired using cardiac-gated Siemens Force or GE Revolution scanners. The closest distance from the stomach or esophagus to the left ventricular (LV) myocardium was measured during both end systole and diastole (Fig 1) using imaging analysis software (Horos Project, Annapolis, MD). Clinical predictors of close proximity were assessed using Student’s t-test, Chi-squared and Pearson’s linear regression.

Results:
In 42 patients (age 65±11.4 years, VT/PVC ablation in 21/42 patients, 50%), the mean gastric proximity was 7.5±4.2mm during end-systole and 6.1±3.6mm during end-diastole (p=0.12). Smaller gastric proximity was significantly associated with increasing LV diameter (y=-1.376*x +12.55; p=0.03) or a history of coronary artery disease (4.8±2.2mm vs 8.3±4.4mm, p=0.02). The closest proximity of the stomach was found most frequently in the mid-segment (compared to the basal or apical segments of the inferior wall, p<0.0001).

Conclusions:
In patients with arrhythmias, the stomach is located within a mean of 6mm to the mid-inferior wall of the LV, with closer proximity in patients with dilated hearts. Careful avoidance of the stomach is critical during radio-ablative therapy of VT to avoid complications, particularly in patients with mid-inferior wall targets and dilated hearts. Studies are ongoing to study motion management strategies to improve precision.
Abstract 11765: Admission to Hospital with Acute Gout is Associated with a Short Term Increased Risk of Major Adverse Cardiovascular Events: A Longitudinal, Population-Level Linked Health Data Study in Western Australia
Authors: Lopez Derrick , NOssent Johannes , Warren Raymond , Preen David , Inderjeeth Charles , Murray Kevin , dwivedi girish , Keen Helen I
Published: March 2022

Introduction:
Cardiovascular disease is the largest contributor to the increased mortality seen in gout. Acute inflammation, which is characteristic of gout, may have a mechanistic role in Major Adverse Cardiovascular Events (MACE).

Hypothesis:
TA temporal relationship exists between admissions to hospital with acute gout, and major adverse cardiovascular events, in a large population based administrative health data set using the self-controlled case series study design

Methods:
Data were extracted from the Hospital Morbidity Data Collection (from 1970) and Death Registrations (from 1969) of the Western Australian Rheumatic Disease Epidemiology Registry. Participants were patients admitted to hospital with first-ever acute gout (ICD-9: 274; ICD-10: M10) between 1990 and 2010 and had an admission or death due to MACE (ICD-9: 410, 411.1, 428, 430-438; ICD-10: I20-I25, I45-I46, I50, I60-169) during the at risk periods (1-10, 11-20 and 21-30 days after acute gout admission) and control period (365 days prior to admissions and 31-365 days after acute gout admission). We used a self-controlled case-series design (within person design which controls for time-constant patient-specific confounding) and performed a conditional fixed-effects Poisson regression to compare the risk of MACE in the at-risk periods to the control periods.

Results:
We identified 835 patients (average age=75.1 years, SD=12.1; 67.4% male) with first-ever acute gout admission and a documented MACE in the control or at-risk periods. An increased risk of MACE was observed in the 1-10 days (Incidence rate ratio [IRR]=3.07, 95%CI: 2.19-4.31), 11-20 days (IRR=2.81, 95%CI: 1.97-4.00), 21-30 days (IRR=1.93, 95%CI: 1.27-2.95) compared to the control period.

Conclusion:
Our self-controlled case series study shows an increased risk of MACE in the first 30 days following a first-ever gout admission and suggests a temporal association between acute inflammation and MACE.
Abstract 11771: Co-Morbid Amyloidosis Leads to Higher In-Hospital Mortality in Patients Undergoing Transcatheter Aortic Valve Replacement: Analysis of National Inpatient Sample
Authors: Almani Muhammad , Usman Muhammad , Collado Fareed Moses , Santos Volgman Annabelle , Ayub Muhammad
Published: March 2022

Introduction:
Amyloidosis is a common comorbidity in elderly patients with aortic stenosis (AS) referred for transcatheter aortic valve replacement (TAVR). We sought to determine the impact of amyloidosis on the clinical outcomes of TAVR.

Methods:
Data were extracted from the National Inpatient Sample (NIS) 2016 - 2018 database. The NIS was searched for adult patients who underwent TAVR during hospitalization with and without amyloidosis as a secondary diagnosis using ICD-10 codes. The primary outcome was inpatient mortality. Secondary outcomes are shown in table 1. Periprocedural complications consisted of intra-operative hemorrhage, accidental rupture and laceration of a circulatory system organ, intra-operative cardiac functional disturbances, intra-operative cardiac functional disturbances and perioperative cerebrovascular infarction. Multivariate logistic and linear regression analysis were used accordingly to adjust for confounders. STATA software was used for analysis.

Results:
Of the148315 patients undergoing TAVR in 2016 - 2018, 150 (0.1%) had secondary diagnosis of amyloidosis. Mean age at the time of TAVR was comparable in both groups (79.4 years, 95% CI 76.5 - 82.3 vs. 79.6 years, 95% CI 79.5 - 79.8; p=0.865). There were 30% females in the amyloidosis group vs. 46% in the other group (p=0.081).The adjusted odds ratio (aOR) for in-hospital mortality for patients undergoing TAVR with comorbid amyloidosis than those without amyloidosis was 4.77 (95% CI 1.06 - 21.49, p=0.042). Patients with amyloidosis had a similar mean difference in length of stay and total hospital charges. Comorbid amyloidosis was not associated with higher odds of peri-procedural cardiovascular complications (aOR: 1.18, 95% CI 0.36 - 3.82, p=0.786). Detailed outcomes are listed in table 1.

Conclusions:
Comorbid amyloidosis leads to higher inpatient mortality but similar rates of peri-procedural cardiovascular complications in patients undergoing TAVR.
Abstract 11775: Association of Hypertension With Mortality in Patients Hospitalised With COVID-19
Authors: Bhatia Kunwardeep S , Sritharan Hari P , Ciofani Jonathan , Allahwala Usaid , Chui Karina , Nour Daniel , Vasanthakumar Sheran , Kandadai Dhanvee , Bhagwandeen Rohan , Brieger David , Choong Christopher , Delaney Anthony , Dwivedi Girish , Harris Benjamin , Hillis Graham , Hudson Bernard , Javorsky George , Jepson Nigel , Kanagaratnam Logan , Kotsiou George , Lee Astin , Lo Sidney , Macisaac Andrew I , McQuillan Brendan , Ranasinghe Isuru , Walton Tony , Weaver James , Wilson William , Yong Andy , Zhu John , van Gaal William , Kritharides Leonard , Chow Clara K , Bhindi Ravinay
Published: March 2022

Introduction:
To assess whether hypertension is an independent risk factor for mortality amongst patients hospitalised with COVID-19 and to evaluate the impact of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) on mortality in patients with a background of hypertension.

Methods:
This observational cohort study included all consecutive index hospitalisations with laboratory proven COVID-19 aged 18 years or older across 21 Australian hospitals entered in the AUS-COVID Registry by 22nd January 2021. Patients were excluded if their past medical or medication history was not available or if they were transferred to another hospital in which case mortality outcomes were not available. Registry data were analysed for in-hospital mortality in patients with comorbidities including hypertension, and baseline treatment with ACE inhibitors or ARBs.

Results:
546 consecutive patients (62.9±19.8 years old, 51.8% male) hospitalised with COVID-19 were enrolled. In the multivariable model, significant predictors of mortality were age (aOR 1.09, 95% CI 1.07-1.12, p<.001), heart failure or cardiomyopathy (aOR 2.71, 95% CI 1.13-6.53, p=.026), chronic kidney disease (aOR 2.33, 95% CI 1.02-5.32, p=.044) and chronic obstructive pulmonary disease (aOR 2.27, 95% CI 1.06-4.85, p=.035) (Figure 1). Hypertension was the most prevalent comorbidity (49.5%) but was not independently associated with increased mortality (aOR 0.92, 95% CI 0.48-1.77, p=.81). Amongst patients with hypertension, ACE inhibitors (aOR 1.37, 95% CI 0.61-3.08, p=.61) and ARBs (aOR 0.64, 95% CI 0.27-1.49, p=.30) did not affect mortality.

Conclusions:
In patients hospitalised with COVID-19, pre-existing hypertension was the most prevalent comorbidity but was not independently associated with mortality. Similarly, the baseline use of ACE inhibitors or ARBs had no independent association with in-hospital mortality.
Abstract 11777: Global Radial Strain Predicts Cardiovascular Events in Patients With Myocarditis Related to the Use of Immune Checkpoint Inhibitors
Authors: Silva Thiago , Awadalla Magid , Hassan Malek , Zafar Amna , Drobni Zsofia , Gongora Carlos , Mahmood Syed S , Zhang Lili , Chen Carol , EDERHY Stephane , Barac Ana , Jones-O'Connor Maeve , Murphy Sean , Coelho-filho Otavio R , Rizvi Muhammad , SAHNI GAGAN , Carlo Gabriele Tocchetti G , Hartmann Sarah , Gilman Hannah , Zatarain-Nicolás Eduardo , Mahmoudi Michael , Gupta Dipti , Michel Caroline , Mansilla Ana Gonzalez , Calles Antonio , Cabral Marcella , Fernandez-Aviles Francisco , Gavira Juan Jose , Gonzalez Nahikari S , Garcia de Yebenes Castro Manuel Y , Afilalo Jonathan , Sullivan Ryan , Ganatra Sarju , Zlotoff Daniel , Yang Eric , Heinzerling Lucie , Thuny Franck , Zubiri Leyre , Reynolds Kerry , Lyon Alexander , Fradley Michael , Thavendiranathan Paaladinesh , Neilan Tomas
Published: March 2022

Introduction:
Myocarditis is as a major immune-related adverse event following the use of immune checkpoint inhibitors (ICI). Global radial strain (GRS) reflects both longitudinal and circumferential fiber shortening but no data exist regarding its utility for diagnosis and risk stratification of ICI-myocarditis.

Hypothesis:
We hypothesized that GRS from echocardiography data would be reduced in patients with ICI-myocarditis and its reduction would have prognostic implications.

Methods:
Leveraging a multicenter international registry, we measured GRS from 76 patients with myocarditis and 49 ICI treated patients with no myocarditis. Pre-ICI GRS values were available for 10 cases and 38 controls. Measures were performed in a central laboratory blinded to group and time (TomTec, Germany). Major adverse cardiac event was a composite of cardiogenic shock, cardiac arrest, complete heart block and cardiac death.

Results:
Groups had similar age (66±15 vs. 63±12 years; p=0.20), sex distribution (male: 72% vs. 61%; p= 0.27) and cancer type (p=0.07). Pre-ICI GRS values were similar between cases and controls (47.4±2.9 vs. 45.4±6.0; p=0.12). A total of 57% of myocarditis patients had LVEF of >50% at presentation. The GRS was lower in patients with myocarditis compared with controls (28.6±6.7 vs. 47±7.4; p<0.01). This lower GRS value was noted in patients with both preserved EF (31.7±5.5 vs. 47.0±7.6, p<0.001) and reduced EF (24.7±6.1 vs. 49.2±4.7, p<0.005). In total, 28 events occurred during a median follow-up of 30 days. In survival analysis, a GRS < the median (29.4%) was associated with an increased rate of events (HR: 3.92, 95% CI: 1.42-10.78, p=0.008) adjusted for age and LVEF. The association between GRS and events was also noted when the variable is treated as continuous adjusted for age and LVEF (HR: 1.07, 95% CI: 1.001-1.15 p=0.04).

Conclusions:
Global radial strain is lower in ICI- myocarditis and the magnitude of the reduction is associated with a higher rate of events.