bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10523: Involvement of Sur2/Kir6.1 In the Physiopathology of Pulmonary Arterial Hypertension
Authors: Le Ribeuz Hélène , Masson Bastien , Dutheil Mary , boet angele , Beauvais Antoine , Sabourin Jessica , Thomas de Montpreville Vincent , capuano veronique , Mercier Olaf M , Humbert Marc , Montani David , Antigny Fabrice
Published: June 2023

Introduction:
The ATP-sensitive K+ channels (KATP) regulatory subunit ABCC8 may be considered a new therapeutic target for pulmonary arterial hypertension (PAH).

Hypothesis:
We hypothesised that the second KATP regulatory subunit (ABCC9) contributes to PAH pathogenesis. ABCC9 gene encodes for two regulatory subunits of KATP channels: the SUR2A and SURB proteins. In the KATP channel, the SUR2 subunits are associated with the K+ channel Kir6.1. We investigated how the SUR2/Kir6.1 channel contributes to PAH pathogenesis and its potential as a therapeutic target against PAH.

Methods:
Using in vitro, ex vivo, and in vivo approaches, we analysed the localisation and expression of SUR2A, SUR2B, and Kir6.1 in pulmonary vasculature of controls and patients with PAH as in experimental PH rat models and its contribution to PAH physiopathology. Finally, we deciphered the consequences of in vivo activation of SUR2/Kir6.1 in the monocrotaline (MCT)-induced PH model.

Results:
We demonstrated that SUR2A, SUR2B, and Kir6.1 were expressed in the lungs of controls and patients with PAH and MCT-induced PH rat model. Myograph experiments showed that activation of SUR2 by pinacidil induced pulmonary arterial relaxation. In vitro experiments on human pulmonary arterial smooth muscle cells and endothelial cells (hPASMCs and hPAECs) in controls and PAH patients showed decreased cell proliferation and migration after SUR2 activation. Using patch-clamp, we demonstrated that SUR2 activation in rat right ventricular (RV) cardiomyocytes reduced RV action potential duration. Chronic pinacidil administration in control rats increased heart rate without changes in hemodynamic parameters. Finally, in vivo pharmacological activation of SUR2 on MCT-induced-PH rats showed an improvement of PH during the preventive and curative protocol.

Conclusions:
We demonstrated that SUR2A, SUR2B, and Kir6.1 were expressed in hPASMCs and hPAECs of controls and PAH patients. In vivo SUR2 activation reduced MCT-induced PH phenotype, suggesting that SUR2 activation should be considered for treatment of PAH.
Abstract 10531: Reactive Hyperemia Index and Coronary Plaque in Asymptomatic Adults - Insights From the Miami Heart Study at Baptist Health South Florida
Authors: Khan Najah , Lahan Shubham , Kwapong Yaa , Sharma Garima , Cainzos Achirica Miguel , Ali Shozab S , Arias Lara , Saxena Anshul , Cury Ricardo C , Budoff Matthew , Feldman Theodore , Blaha Michael J , Fialkow Jonathan , Nasir Khurram
Published: June 2023

Objective:
We aimed to evaluate the associations between the reactive hyperemia index (RHI), a non-invasive estimate of endothelial function, and coronary artery plaque presence and features on coronary computed tomography angiography (CCTA); and whether these associations differ by sex.

Methods:
Data from Miami Heart Study, an ongoing, prospective US cohort of individuals free of clinical ASCVD. A total of 2,097 participants underwent assessment of both RHI using EndoPAT® (abnormal RHI defined as <1.67) and a CCTA scan. We computed the unadjusted prevalence of 4 plaque outcomes (any coronary plaque on CCTA, CAC score >0, maximal coronary stenosis ≥50%, and presence of ≥1 high-risk plaque features) among individuals with and without abnormal RHI; overall and by sex. Multivariable logistic regression models were used to investigate the association between RHI and the outcomes adjusting for confounders, overall and by sex.

Results:
Of the 2,097 participants, mean age was 53 years, 50% were women, and 15% had abnormal RHI. Mean age was 54±7 vs. 53±7 years for normal vs. abnormal RHI, respectively, and 17% men vs 13% women had abnormal RHI. In unadjusted analyses, abnormal RHI was not associated with a significant higher prevalence of any of the study outcomes (
Figure Panel A
; all P >0.05). Adjusting for sociodemographics, no statistically significant associations were observed between abnormal RHI and any of the coronary plaque features evaluated (
Panel B
). Similar observations were noted further adjusting for other risk factors. There was no evidence of interaction by sex in any of the associations (P for interaction: all >0.05).

Conclusions:
In the Miami Heart Study, abnormal RHI measured using EndoPAT was not associated with coronary plaque in either women nor men. Our findings suggest that this measurement may be suboptimal in the assessment of endothelial function, and not informative in predicting the presence of subclinical coronary atherosclerosis.
Abstract 10533: Cardiorenal Effects of Sglt2 Inhibitors and Finerenone in Type 2 Diabetes and Chronic Kidney Disease. Single, Dual or Triple Therapy? A Network Meta-Analysis
Authors: Diaz Acevedo Jesus , Lazcano Greilys , Soto Mariana , Castro Adela , Penaherrera Carlos , Buitrago Andres F , PUNCHAYIL NARAYANANKUTTY NAVEEN , Navas Viviana , Pino Jesus E
Published: June 2023

Introduction:
Sodium-glucose co-transporter 2 inhibitors (SGLT2i) and a non-steroidal mineralocorticoid receptor antagonist, finerenone, have demonstrated their efficacy in slowing CKD progression and preventing cardiovascular events in diabetic kidney disease (DKD). However, it is unclear which one is more effective or whether a combination could provide additional benefits.

Methods:
A network meta-analysis (NMA) was conducted on RCTs of DKD, which evaluated the cardiovascular and renal effects of SGLT2i and finerenone. The primary outcome was a cardiorenal outcome composed of GFR decline as defined in original RCTs, end-stage kidney disease (ESKD), heart failure hospitalization (HHF), and death from renal and cardiovascular causes.

Results:
This NMA comprised 4 RCTs and 61,609 patient-year with DKD. Dual therapy with SGLT2i+RAASi or finerenone+RAASi was more effective than single therapy with RAAS inhibition (RAASi) for the risk reduction of the cardiorenal composite HR 0.67 (95% CrI 0.60 - 0.74) and 0.81 (95% CrI 0.75 - 0.89), respectively. The dual therapy with SGLT2i+RAASi was superior to finerenone+RAASi HR 0.82 (95% CrI 0.72 - 0.94) for the reduction of cardiorenal events (Table 1). The triple therapy (SGLT2i+finerenone+RAASi) vs RAASi showed a 46% relative risk reduction (HR 0.54 95% CrI 0.5 - 0.58) for the cardiorenal composite. Finerenone+RAASi was most likely to lead to discontinuation of therapy due to hyperkalemia HR 2.83 (95% CrI 1.96 - 4.08) when compared to RAASi, however, it was not notice when compared to triple therapy HR 2.83 (95% CrI 0.83 - 9.62). All therapies reduced the risk of all-cause death as follows finerenone+RAASi (HR 0.88, 95% CrI 0.80 - 0.98), SGLT2i+RAASi HR 0.78 (95% CrI 0.66 - 0.91) and SGLT2i+finerenone+RAASi HR 0.69 (95% CrI 0.63 - 0.75).

Conclusion:
This NMA suggests that triple therapy with SGLT2i+finerenone+RAASi is superior in reducing cardiorenal events compared to single or dual therapy with a similar safety profile.
Abstract 10566: Hypothermia as an Adjunctive Therapy to Percutaneous Intervention in St-Elevation Myocardial Infarction: A Systematic Review and Meta-Analysis of Randomized Control Trials
Authors: Mhanna Mohammed , Ranabothu Meghana , Beran Azizullah , Al-Abdouh Ahmad , Jabri Ahmad , Sajdeya Omar , Barbarawi mahmoud , Al-Aaraj Ahmad , Eltahawy Ehab
Published: June 2023

Introduction:
In the setting of acute ST-elevation myocardial infarction (STEMI), several randomized control trials (RCTs) suggested a potential benefit with the use of Therapeutic hypothermia (TH). However, results from previous studies are contradictory.

Method:
We performed a comprehensive literature search for studies that evaluated the efficacy and safety of adjunctive TH compared to the standard percutaneous coronary intervention (PCI) in awake patients with STEMI. The primary outcome was the infarct size (IS) and microvascular obstruction (MVO) assessed by cardiac imaging at the end of follow-up. The secondary outcomes were major adverse cardiovascular events (MACE), procedure-related complications, and door to balloon time. Relative risk (RR) or the mean difference (MD) and corresponding 95% confidence intervals (CIs) were calculated using the random-effects model.

Results:
A total of 10 RCTs, including 706 patients (mean age: 58±9.6 years, 364 patients managed with adjunctive TH vs. 342 with standard PCI), were included. As compared to standard PCI, TH was not associated with a statistically significant improvement in the IS (MD: -0.87 %, 95%CI: -2.97, 1.23; P = 0.42) or in the MVO (MD: 0.11 %, 95%CI: -0.06, 0.27; P = 0.21). MACE and its individual components were comparable between the two groups. However, the TH approach was associated with an increased risk of infection and prolonged door to balloon time. Furthermore, there was a trend in the TH group toward an increased incidence of stent thrombosis and paroxysmal atrial fibrillation.

Conclusions:
According to our meta-analysis of published RCTs, the benefit of TH in STEMI patients is modest, with a marginal safety profile and potential for care delays. Larger-scale RCTs are needed to further clarify our results.
Abstract 10570: Inflammation During Early Post-Acute Covid-19 is Associated With Reduced Exercise Capacity and Long Covid Symptoms After 1 Year
Authors: Durstenfeld Matthew S , Peluso Michael J , Kaveti Punita , Hill Christopher , Li Danny , Sander Erica , Swaminathan Shreya , Arechiga Victor M , Sun Kaiwen , Ma Yifei , zepeda victor , Lu Scott , Goldberg Sarah A , Hoh Rebecca , Chenna Ahmed , Yee Brandon C , Winslow JOhn W , petropoulos christos J , Win Sithu , KELLY JOHN D , Glidden David V , Henrich Timothy J , Martin Jeffrey N , Lee Yoo Jin , Aras Mandar A , Long Carlin S , Grandis Donald J , Deeks Steven G , Hsue Priscilla Y
Published: June 2023

Introduction:
Mechanisms underlying cardiopulmonary symptoms following SARS-CoV-2 infection (post-acute sequelae of COVID-19 “PASC” or “Long COVID”) remain unclear. The purpose of this study was to elucidate the pathophysiology of PASC using cardiopulmonary exercise testing (CPET), cardiac magnetic resonance imaging (CMR) and ambulatory rhythm monitoring.

Methods:
We performed CMR, CPET, and ambulatory rhythm monitoring among adults > 1 year after confirmed SARS-CoV-2 infection in the UCSF Long-Term Impact of Infection with Novel Coronavirus cohort (LIINC; NCT04362150) and correlated findings with previously measured biomarkers. We used logistic regression to estimate associations with PASC symptoms and linear regression to estimate differences by symptoms adjusted for confounders.

Results:
Out of 120 participants, 46 participants (unselected for symptom status) had cardiac testing performed at median 17 months after infection. Median age was 52, 18 (39%) were female, and 6 (13%) were hospitalized for severe acute infection. On CPET (n=39), 13/23 (57%) with symptoms had reduced exercise capacity (peak VO2<85% predicted) compared to 2/16 (13%) without symptoms (p=0.008). Adjusted peak VO
2
was 5.9 ml/kg/min lower (-9.6 to -2.3; p=0.002) or -21% predicted (-35 to -7; p=0.006) among those with symptoms. Chronotropic incompetence was present among 9/15 (60%) with reduced peak VO2 (adjusted heart rate reserve<80%: OR 15.6 for reduced peak VO2, 95%CI 1.30-187; p=0.03). Inflammatory markers (hsCRP, IL-6, TNF-α) and SARS-CoV-2 antibody levels measured early in PASC (median 3.5-6 months after infection) were negatively correlated with peak VO2 more than 1 year later (Figure).

Conclusions:
Cardiopulmonary symptoms and elevated inflammatory markers present early in PASC are associated with reduced exercise capacity during CPET >1 year following COVID-19. Chronotropic incompetence may explain reduced exercise capacity among some individuals with PASC.
Abstract 10571: Causes of Early Mortality After Catheter Ablation of Ventricular Tachycardia in Patients With Reduced Left Ventricular Ejection Fraction
Authors: Tan Min Choon , Lee Justin Z , Deshmukh Abhishek , Srivathsan Komandoor , Shen Win K , El Masry Hicham , Scott Luis , Asirvatham Samuel , Cha Yong-Mei , McLeod Christopher J , Mulpuru Siva K
Published: June 2023

Background:
Recognition of the causes of early mortality after ventricular tachycardia (VT) ablation in patients with reduced left ventricular ejection fraction is an essential step toward improving post-procedural outcomes.

Objective:
This study sought to determine the causes of early mortality (≤30-days) after VT ablation in patients with reduced left ventricular ejection fraction and to understand further the circumstances surrounding death after the procedure.

Methods:
We performed a retrospective analysis of all patients undergoing VT ablation in patients with reduced left ventricular ejection fraction from January 1, 2013, to November 10, 2021, at the Mayo Clinic (Rochester, Phoenix, and Jacksonville). Causes of death were identified through a detailed chart review of the electronic health record within the Mayo Clinic system and outside records.

Results:
A total of 503 patients (mean age 63 ± 13 years, 11.2% female) with EF <50% were included in the study. The 30-day all-cause mortality rate was 5% (n=25), and the mortality rate due to a procedural complication was 0.4%. Among all 30-day deaths, recurrent VT was the most common primary cause of death (44%). This was followed by decompensated heart failure (28%), procedure-related death (8%), cerebrovascular accident (CVA) (4%), and infection (4%). Most patients (91%) who died from VT had the VT recurrence within three days of the ablation. 76% of patients with early mortality had delayed referral for VT ablation, and 72% opted for comfort care before death.

Conclusions:
The overall early mortality (≤30-days) rate after catheter ablation of VT in patients with reduced left ventricular ejection fraction was 5%, but the death rate directly due to a procedural complication was only 0.4%. The most common cause of death was recurrent VT, followed by heart failure. Further research into ablation strategies is vital to improving the safety, efficacy, and durability of VT ablation.
Abstract 10572: Awareness and Feasibility of Women Chairing Cardiology Sessions in Scientific Meetings: A Nationwide Survey by the Japanese Circulation Society
Authors: Nakayama Atsuko , Kamiya Chizuko A , Kanki Sachiko , Ide Tomomi , Bando Yasuko K , Uemura Yukari , Tsukada Yayoi T
Published: June 2023

Introduction:
Diversity and inclusion remain a concern in the field of cardiology. Female cardiologists have less opportunity to chair sessions in scientific meetings than men. However, cardiologists’ awareness and perspectives on feasibility of chairing sessions is poorly understood.

Methods:
A web-based survey on awareness regarding the commitment of chairing sessions was sent to 14,798 certificated cardiologists registered with the Japanese Circulation Society (JCS).

Results:
A total of 3,412 valid responses were obtained, including 523 women and 2,889 men. Female cardiologists exhibited less interest in serving as chairpersons in Japanese and English sessions (71% women vs. 82% men, P<0.001, 30% women vs. 40% men, P<0.001). Influencing factors of chair acceptance in Japanese sessions for female cardiologists were being a cardiologist for over 10 years (odds ratio [OR] 1.84, 95% confidence interval [CI] 1.02-3.33), experience studying abroad (OR 3.35, 95%CI 1.93-5.81) and chairing sessions (OR 8.39, 95%CI 5.48-12.9), having a Doctor of Philosophy (OR 2.82, 95%CI 1.09-7.31), presence of four or more female cardiovascular specialists in the hospital (OR 1.70, 95%CI 1.10-2.61) and of role models (OR 2.86, 95%CI 1.93-4.24), and awareness of the JCS chairperson’s manual (OR 10.7, 95%CI 6.67-17.1). The receiver operating characteristic curve revealed that the number of female cardiovascular specialists in a hospital was a more sensitive predictor of chair acceptance among male than female cardiologists.

Conclusions:
Female cardiologists were less likely to accept chairing sessions compared with male cardiologists and the presence of female cardiovascular specialists positively influenced chair acceptance.
Abstract 10574: Disrupted Sleep is Associated With Increased 24-Hour Systolic Blood Pressure Variability in Caregivers
Authors: Ahn Soojung , Esquivel Jill H , Davis Eric M , Chung Misook L , Lobo Jennifer M , Logan Jeongok G
Published: June 2023

Introduction.
A growing body of research shows an association between caregiving and increased cardiovascular disease (CVD) risk. Blood pressure variability (BPV) is known as a surrogate marker of CVD development. However, BPV in caregivers has rarely been used to assess for CVD risk, especially in relation to psychological and behavioral factors. The purpose of this study was to examine the associations of psychological symptoms (i.e., caregiving burden and depressive symptoms) and sleep quality with 24-hour BPV among caregivers of individuals with chronic illness.

Methods.
Thirty caregivers (25 female; 27 non-Hispanic white; mean age 62 years) who provided in-home care were recruited from the community in this cross-sectional study. Caregiver demographic data, caregiving stress (Zarit Burden Interview), and depressive symptoms (Patient Health Questionnaire-9) were obtained. Sleep quality (i.e., sleep efficiency, wake after sleep onset, the number of awakenings) was assessed using an actigraph for 7 consecutive days. Systolic and diastolic BPV over 24 hours, while awake (daytime), and while sleeping (night time) were obtained by ambulatory BP monitoring. Pearson's correlations and multiple linear regression were conducted to examine associations of psychological symptoms and sleep quality with BPV.

Results.
Sleep efficiency was negatively correlated with diastolic BPV while awake (
r
= -0.368,
p
= 0.045). The number of awakenings during sleep was positively correlated with systolic BPV while awake (
r
= 0.426,
p
= 0.019) and diastolic BPV while awake (
r
= 0.422,
p
= 0.020). Caregiving stress and depression were not correlated with BPV. After controlling for age and mean arterial pressure, the number of awakenings was associated with increased systolic BPV over 24 hours (
B
= 0.194,
p
= 0.018) and systolic BPV while awake (
B
= 0.280,
p
= 0.002), respectively.

Conclusion.
Caregivers’ disrupted sleep represented by frequent awakenings may play a role in increased CVD risk as evidenced by increased BPV. While future large clinical studies should be conducted to confirm these findings, improving sleep quality would need to be considered for CVD prevention strategies for caregivers.
Abstract 10583: A Critical Contribution of Cardiac Myofibroblasts in Rv Failure and the Role of Ucp2 Snps in the Predisposition to Rv Decompensation in Pulmonary Arterial Hypertension
Authors: Zhang Yongneng , Lorenzana Carrillo Maria A , Mohseni Mahsa , Tejay Saymon , Liu Yongsheng , Haromy Alois S , Sutendra Gopinath , Michelakis Evangelos D
Published: June 2023

Introduction:
The compensatory stage in right ventricle hypertrophy (RVH) in pulmonary arterial hypertension (PAH) is much shorter than in left ventricle hypertrophy (LVH) in systemic hypertension. Between 2 patients with the same degree of PAH one may have a much shorter compensated RVH (cRVH) stage than the other. The cardiac myofibroblasts (CMF) may contribute to these differences. Their ability to contract (stiffening), produce collagen and promote inflammation contributes to heart failure. Decreased mitochondrial calcium (mCa++) promotes CMF differentiation (from cardiac fibroblasts). Methylation of the mCa++ Uptake 1 (MICU1) and lack of UCP2 (uncoupling protein 2, a component of the mCa++ uniporter complex) activate CMF in the LV.

Hypothesis:
RV CMF are major contributors to RV failure in PAH, and loss of CMF-UCP2 promotes myofibroblast activation and RV decompensation.

Methods:
In a rat PAH model (Monocrotaline-PAH), we measured the RV pressure from isolated perfused hearts and sarcomere shortening from isolated RV cardiomyocytes. In a cohort (n=25) of patients with pulmonary hypertension that had been treated with the same protocol for years and controlled for age/sex/duration of disease, the correlation between UCP2 loss-of-function SNPs and RV function was measured.

Results:
In isolated hearts, RV pressure is lower in decompensated RVH (dRVH) compared to normal RV, but in vitro there is no difference in cardiomyocyte sarcomere shortening between the two groups, pointing to potential detrimental role of RV CMF rather than contractile failure of RV cardiomyocytes. dRVH has much more CMF compared to normal RV. CMF from dRVH have increased MICU1 methylation and decreased UCP2 levels compared to normal RV fibroblasts. PAH patients with homozygotes for UCP2 SNPs have worse RV function compared to heterozygote or wild-type, despite similar PA pressures.

Conclusions:
Our preliminary work suggests that RV CMF rather than RV cardiomyocytes may drive RV decompensation independent of RV afterload in PAH patients and this may be predicted by UCP2 SNPs that are relatively frequent in the population and have been shown to be associated with PAH outcomes (10-year survival, time to transplantation).
Abstract 10591: Psychometric Testing of the Left Ventricular Assist Device Self-Care Behaviour Scale
Authors: Kato Naoko P , Melnikov Semyon , Denfeld Quin E , Casida Jesus , Stromberg Anna , Ben Gal Tuvia , Lee Christopher S , Jaarsma Tiny
Published: June 2023

Introduction:
Adequate self-care behaviour is essential for patients with a left ventricular assist device (LVAD) to prevent complications, prolong life, and optimise quality of life. However, this field has lacked valid and reliable measures to assess self-care behaviour among patients with LVAD. To address this need, we recently developed the 33-item LVAD self-care behaviour scale based on a literature review and 2-round Delphi method.

Objectives:
To evaluate psychometric properties of the new 33-item LVAD self-care behaviour scale.

Methods:
A cross-sectional survey using a self-administered questionnaire was performed in Japan, Israel, and the United States. Measurement properties of the LVAD self-care behaviour scale were evaluated in reference to the COSMIN Study Design Checklist. In the present study, construct validity, convergent validity, internal consistency, and test-retest reliability were examined. Test-retest reliability was evaluated in a subsample of data (n = 18) from the first and second surveys.

Results:
Data on 127 patients with LVAD in Israel, Japan, and the USA were analysed (mean age 51±14.3, 81% male). Approximately half had a HeartMate II (47%), while 20% had a HeartMate 3. The median time patients lived with the LVAD was 9.7 months [IQR 3.9-21.8]. Exploratory factor analysis with promax rotation extracted three factors [Factor 1: Monitoring (8 items), Factor 2: Heart failure self-care (5 items), and Factor 3: LVAD self-care (7 items)], and during the analysis 13 items were excluded from the scale. Internal consistency assessed by Cronbach’s alpha was acceptable for the total scale (α=0.80) and the three subscales: Monitoring (α=0.81), Heart failure self-care (α=0.67), and LVAD self-care (α=0.63). The 20-item version of the LVAD self-care behaviour scale had sufficient convergent validity with the LVAD Patient Home Management Adherence Scale (r=0.47, p<0.001). The intraclass correlation coefficient of the total score was 0.58, suggesting adequate test-retest reliability.

Conclusions:
The 20-item version of the LVAD self-care behaviour scale showed adequate validity and reliability. The scale is ready for use in clinical practice and research. Additional testing might further optimise the scale.
Abstract 10603: Dapagliflozin Increases Ampk, Reduces Fibrosis/Hypertrophy and Nlrp-3, Il-6 and Galectin-3 Levels in Short-Term Doxorubicin-Treated Mice Improving Cardiac Function
Authors: Maurea Nicola , Buccolo Simona , Bisceglia Irma , Canale Maria Laura L , Luciano Antonio , Barbieri Antonio , Palma Giuseppe , Scherillo Marino , Quagliariello Vincenzo
Published: June 2023

Introduction:
Doxorubicin-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in breast cancer patients. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently been shown to be of therapeutic value in patients with type 2 diabetes, chronic kidney disease, and heart failure with reduced ejection fraction (HFrEF), conditions that commonly coexist and are interrelated pathophysiologically.

Hypothesis:
Dapagliflozin (an SGLT2i), administered during doxorubicin, could improve cardiac function in preclinical models

Methods:
Female C57Bl/6 mice were untreated (Sham, n=6) or treated for 10 days with doxorubicin i.p at 2.17 mg/kg (DOXO, n=6), DAPA at 12 mg/kg (DAPA, n=6) or doxorubicin combined to DAPA (DOXO-DAPA, n=6). Ejection fraction, radial and longitudinal strain were analyzed through transthoracic echocardiography (Vevo 2100). Cardiac tissue expression of NLRP3 inflammasome, Myd88, DAMPs (galectine 3 and calgranulinS100) , pAMPK, NF-kB, and 13 chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified through ELISA and western blot methods.

Results:
DAPA improved significantly the EF and prevented the reduction of radial and longitudinal strain after 10 days of treatment with doxorubicin. A reduced expression of NLRP3, MyD88, DAMPs and NF-kB in cardiac tissues was seen in DOXO-DAPA group compared to DOXO mice (p<0.001). Cardiac expression of IL-1β, IL-6, TNF-α, G-CSF and GM-CSF were significantly reduced after treatment with DAPA indicating anti-inflammatory properties. Expression of pAMPK was strongly enhanced in DAPA-DOXO compared to DOXO group. Levels of Calgranulin S100 and galectine-3 were strongly enhanced in DOXO group; on the other hand their expression were reduced by 47.7 and 52.3% in DAPA-DOXO group vs DOXO (p<0.005). Hystology evaluation indicate reduction in hypertrophy, fibrosis and cardiac necrosis in DOXO-DAPA vs DOXO.

Conclusions:
DAPA is able to improve cardiac function and reduce biomarkers involved in heart failure and fibrosis. The overall picture of the study pushes the use of DAPA in prevention of cardiomyopathies induced by anthracyclines in cancer patients.
Abstract 10620: CD271 Expression Enhances Angiogenic Capacity in Human Adipose-Derived Stem Cells
Authors: Hashimuko Daiki , Inoue Oto , Usui Soichiro , Nomura Ayano , Yamaguchi Kosei , Takeda Yusuke , Goten Chiaki , Takashima Shinichiro , Sakata Kenji , Iino Kenji , Takemura Hirofumi , Takamura Masayuki
Published: June 2023

Introduction:
Therapeutic angiogenesis using stem cell transplantation can be a novel strategy for ischemic disease. Recently, stem cells with gene modifications have been considered as an option to boost therapeutic efficacy. Surface receptor CD271 has emerged as a useful marker for proliferative or angiogenic cell isolation from human organs. We hypothesized CD271 expression on adipose-derived stem cells (ADSCs) would increase their angiogenic capacity.
Purpose:
We aimed to assess in vitro and in vivo angiogenic capacity of CD271-over expressed human ADSCs.

Methods:
ADSCs were established from human adipose tissue from healthy subjects and transfected with lentiviral vector for CD271 overexpression (OE-ADSCs). Vector transfection was performed with previously reported method using protamine. Vector without CD271 gene insert was used to prepare control (Cont-ADSCs,
Fig.A
). Overexpression of CD271 was evaluated by qPCR and flow cytometry after cell selection using puromycin. For in vivo angiogenic capacity, ADSCs were prelabeled with PKH26 living cell dye, injected via intra-muscular injection into mice subjected to limb ischemia model, and evaluated by immunohistochemistry of ischemic limb (gastrocnemius).

Results:
We found that mRNA expression of CD271 was 10,000-fold higher in OE-ADSCs than in Cont-ADSCs. Consistently, over 90% of OE-ADSCs expressed CD271 protein. (
Fig.B
). Overexpression of CD271 on ADSCs increased mRNA expression of angiogenic factors such as
VEGFA
and
CXCL12
. Furthermore, mRNA expression of TIMP2, anti-angiogenic factor, was significantly decreased in OE-ADSCs (
Fig.C
). In cell therapy, we demonstrated that administration of OE-ADSCs enhanced in vivo angiogenic capacity evaluated by capillary density. Notably, ADSC engraftment capacity was also augmented in OE-ADSCs (
Fig.D
).

Conclusion:
These findings highlight the important role of CD271 expression on ADSCs for their angiogenic gene profile and cell therapy effects.
Abstract 10643: Anticoagulation Prescriptions for Patients With Acute Precipitants of Atrial Fibrillation in the VITAL-AF Study
Authors: Hardie Lakotah , Venn Rachael , Chang Yuchiao , Ashburner Jeffrey M , Khurshid Shaan , Shea Marisa , McDermott Steven , Borowsky Leila H , McManus David D , Atlas Steven , Ellinor Patrick T , Singer Daniel E , Lubitz Steven A
Published: June 2023

Introduction:
Many patients with incident atrial fibrillation (AF) are diagnosed in the setting of a potentially transient precipitant. Despite substantial rates of AF recurrence and stroke in this population, prior registries and survey data suggest lower usage of oral anticoagulants (OAC). Here, we examined use of OAC on the basis of precipitated versus non-precipitated AF among patients enrolled in the VITAL-AF trial.

Methods:
VITAL-AF (clinicaltrials.gov NCT03515057) was a cluster randomized trial of 16 primary care practices evaluating point-of-care AF screening using single-lead ECGs among individuals aged ≥ 65 years (n=30,715). The primary outcome of newly diagnosed AF at one year occurred in 503 patients. For each incident AF event, we performed manual chart review to classify if diagnosis occurred in the setting of an acute precipitant, if the episode was transient, and if OAC was initiated. AF was considered transient if there was documented return to sinus rhythm within three months of initial diagnosis. OAC initiation required both evidence of a new prescription and corresponding provider documentation

Results:
Of the 503 cases of incident AF diagnosed during the VITAL-AF study period, 125 (24.9%) occurred in the setting of an acute precipitant. The mean age of patients with newly diagnosed AF was 78.3 ± 9.0 years, 46% were female, 11% were non-white, and the mean CHA
2
DS
2
-VASc score was 4.2 ± 1.6, which were similar between those with and without a precipitant. Patients with acute precipitants of AF were more likely to have transient episodes (94% vs 76%, p=0.001) and less likely to be started on OAC (60% vs 82%, p<0.001) than patients without a precipitant. In a multivariable model adjusted for age, race, gender, CHA
2
DS
2
-VASc score, study arm, and screening status, AF occurring in the context of a precipitant was associated with significantly decreased odds of OAC initiation (odds ratio [OR] 0.32, 95% CI [0.20, 0.52]).

Conclusions:
Patients diagnosed with precipitated AF are more likely to have transient episodes with return to sinus rhythm within three months of diagnosis and less likely to be started on OAC compared to patients without a precipitant. Future analyses examining the effectiveness of OAC among patients with precipitated AF are warranted.
Abstract 10669: Phenytoin, an Anti-Epileptic Sodium Channel Blocker, May Be a Novel Therapy for Type 3 Long Qt Syndrome Mediated by the Lidocaine-Insensitive SCN5A-F1760C Variant
Authors: Ye Dan , Stutzman Marissa , Kim Maengjo , Gluscevic Martina , Zhou Wei , Gao Xiaozhi , Tester David J , Giudicessi John , Shannon Kevin , Ackerman Michael J
Published: June 2023

Introduction:
Gain-of-function mutations in
SCN5A-
encoded cardiac sodium channel (Na
V
1.5) cause type 3 long QT syndrome (LQT3). Patients with SCN5A variants localizing to the local anesthetic binding domain might not be sensitive to lidocaine or mexiletine treatment.

Hypothesis:
Phenytoin, a sodium channel blocker used to treat epilepsy, may be a novel LQT3-directed therapy for a variant involving a critical residue of the Nav1.5’s local anesthetic binding domain.

Methods:
SCN5A-F1760C was identified in a now deceased infant with severe LQT3 (QTc of 680-1200 ms) who was refractory to left cardiac sympathetic denervation and pharmacological treatments with either lidocaine or mexiletine. SCN5A-F1760C was engineered by site directed mutagenesis and expressed in TSA201 cells. Patient-specific pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from the SCN5A-F1760C-positive infant and gene-edited/variant-corrected isogenic control (IC) iPSC-CMs were generated. Na
V
1.5 currents were recorded in TSA201 cells transfected with SCN5A-WT/ F1760C and action potentials (APs) from iPSC-CMs were recorded before and after treatment with 5μM Phenytoin using the whole cell patch-clamp technique.

Results:
SCN5A-F1760C did not change the NaV1.5 current density. However, the V1/2 of inactivation was right-shifted significantly by +14.1 mV from -86.3±0.9 mV (WT) to -72.2±0.7 mV (F1760C, p<0.0001) resulting in a marked increase in window current. F1760C increased sodium late current 2-fold from 0.18±0.04% in WT to 0.49±0.07% in F1760C (p=0.0005). Baseline APD to 90% repolarization (APD90) was prolonged significantly in F1760C-derived iPSC-CMs (641±40 ms) compared to IC iPSC-CMs (412±22 ms, p<0.0001). Treatment with 5μM phenytoin normalized the APD90 in F1760C-derived iPSC-CMs to 423+34 ms (p<0.0001), values approximating the ‘gene/variant-edited’ cure.

Conclusions:
Na
V
1.5 gain-of-function caused by a novel SCN5A-F1760C variant results in marked APD90 prolongation which were rescued by phenytoin indicating the antiepileptic drug, phenytoin, may be a mutation-specific, LQT3-directed therapy for those LQT3-causative variants that disrupt the local anesthetic/lidocaine-binding domain.
Abstract 10677: A Systems Biology Approach Demonstrating the Association Between Mir 122-5p and Glutamine Metabolism With Cardiovascular Health in Black Adults: Results From the Morehouse-Emory Cardiovascular (meca) Center for Health Equity
Authors: Islam Shabatun , Liu Chang , Beydoun Nour , Mohandas Appesh N , Rooney Kimberly , Nayak Aditi , Mehta Anurag , Taylor Herman A , Sun Yan , Jones Dean , Quyyumi Arshed A , Searles Charles D
Published: June 2023

Intro:
Integrative analysis of extracellular microRNA (miRNA) and metabolomics is a novel approach to identifying molecular pathways underlying cardiovascular health (CVH). Levels of miRNAs are linked to cardiovascular disease (CVD), while cardiometabolic risk factors are known to alter activity of select metabolic pathways. We identified miRNAs and metabolites underlying CVH in a cohort of Black adults through an integrative analysis of extracellular miRNA levels, metabolite concentrations and clinical factors associated with CVH.

Methods:
The MECA cohort consisted of 371 Black adults (age 53+10, 38.5% male) without known CVD. CVH was determined by Life’s Simple 7 (LS7) score, calculated from blood pressure, fasting glucose, cholesterol, BMI, exercise, diet, and smoking. Metabolite concentrations in plasma was assessed by high-resolution metabolomics profiling, and expression of miRs-122-5p, -150-5p, and -30c-5p was assessed by RT-qPCR. Metabolome wide association study (MWAS) identified metabolites associated with LS7. Association of miRNA levels with CVH clinical domains was assessed using Spearman correlation. Integrative analysis of select miRNAs, metabolites, and CVH clinical domains was performed using the program xMWAS.

Results:
Expression of 30 metabolites was associated with improved CVH (FDR<0.2) where glutamine was higher (p=0.005), and glutamate was lower (p<0.001). Integrative analysis showed association between miR-122-5p, glutamine and fasting glucose. miR-122-5p expression independently correlated with fasting glucose (p=0.03) and glutamine/glutamate is known to be associated with glucose metabolism. In silico and in vitro analyses revealed glutamine synthetase as a potential target of miR-122-5p (Fig).

Conclusions:
We demonstrate novel associations between glutamine, miR-122-5p and fasting glucose in CVH, suggesting that select metabolites and miRNAs are markers of CVH and maybe potential therapeutic targets.
Abstract 10721: Pharmacologic Management of Bradycardia During Rotational Atherectomy: A 10-Year Veterans Affairs Experience
Authors: Minchak Megan , Ramsayer Emily , Mostertz William C , Evans Matthew C , Keck Carson M , Robinson Nodia , Aldridge Marissa , Nielsen Chris , Fernandes VALERIAN , Maran Anbukarasi
Published: June 2023

Introduction:
Rotational atherectomy (RA) is frequently used for plaque modification in patients with calcified coronary lesions. RA use in dominant artery lesions is often associated with transient bradyarrhythmias, thought to be due to adenosine release from injured erythrocytes. As such, prophylactic transvenous pacemakers (TVP) are often placed, increasing risk of bleeding and tamponade. We hypothesize that patients undergoing RA at risk for bradyarrhythmias can be safely managed with non-selective adenosine receptor antagonists without routine prophylactic TVP use.

Methods:
We retrospectively identified 384 consecutive patients who underwent RA at the Ralph H. Johnson VA Medical Center between January 2011 and September 2020. Patients were divided into those pretreated with aminophylline or theophylline (n=147) and those who were not. Primary and secondary endpoints were breakthrough bradyarrhythmia requiring acute pharmacologic or TVP rescue and a composite of 30-day cardiovascular mortality, readmission, and permanent pacemaker implantation.

Results:
A total of 319 patients who underwent 358 RA procedures met our inclusion criteria. None of the patients had a prophylactic TVP. Overall, 25 patients (6.9%) developed bradycardia, all successfully managed pharmacologically without TVP rescue. Of those pretreated, significantly more patients (12.2%) developed breakthrough bradycardia compared to the 3.3% that did not receive pretreatment (P value 0.001). RA on a dominant vessel was the only significant risk factor among those who developed bradycardia. There was no difference in the secondary endpoint between those pretreated with a non-selective adenosine receptor antagonist compared to those that were not (P value 0.09).

Conclusion:
Plaque modification with RA can be safely done without routine prophylactic TVP use with favorable acute procedural and short-term outcomes with aminophylline or theophylline pretreatment. There is a significant risk of breakthrough bradycardia with RA on a dominant vessel that can be easily managed medically.
Abstract 10732: Independent Evaluation of Effects of a Virtual Employer-Sponsored Type 2 Diabetes Management Program on Blood Glucose
Authors: Chen Zhen , Birse Charles E , Fragala Maren , Mcphaul Michael J , Bare Lance
Published: June 2023

Objective:
To evaluate the effect of an employer-sponsored T2D management virtual program (Onduo) on blood glucose changes, via an independent data source, within the first year of participation.

Methods:
This retrospective pre-post study included participants with T2D who engaged in Onduo Dec 2020-Sept 2021. Participants had to have completed an employer-sponsored wellness program (independent of Onduo) with year-end biometric screening in 2019, 2020 and 2021, which included HbA1c, fasting glucose (FG), lipids, and other biometric measurements (Table). Year-to-year changes pre-intervention (2019 vs 2020 wellness screening, before Onduo) and post-intervention (2020 vs 2021) were compared using paired t-tests (significant at
P
≤.05). We also assessed year-to-year changes based on use of specific Onduo telehealth tools (mobile app, blood glucose meter [BGM], health coach consultations, continuous glucose monitor [CGM], and telemedicine visits).

Results:
All 578 participants included (Table) used a mobile app, 84% used personalized coaching, 69% BGM, 13% telehealth visits, and 10% CGM. Seventy (12.1%) participants had HbA1c ≥9% in 2019, 79 (13.7%) in 2020, and 57 (9.9%) in 2021 (2019 vs 2020:
P
=.3; 2020 vs 2021:
P
=.01;

Χ
2

tests). Within the first year of intervention, year-to-year changes in HbA1c, FG, HDL, and LDL significantly improved compared to pre-intervention changes (Table). The largest glycemic improvements post-intervention were in participants with baseline HbA1c ≥9% (
P
<.001; ANOVA) or baseline FG ≥126 mg/dL (
P
<.001; 2-sample t-test). Participants who used a CGM or telemedicine visits (n=81) had greater post-intervention drops (2020 vs 2021) in HbA1c than did others (-0.7 vs -0.2%,
P
<.01; 2-sample t-test).

Conclusions:
Participation in Onduo improved year-to-year trends in HbA1c, FG, HDL, and LDL. Improvements in glycemia were greater in participants with the highest baseline glycemic indices and those who used a CGM or telemedicine visits.
Abstract 10746: Association of Left Ventricular Relative Wall Thickness With Thromboembolism in Non-Valvular Atrial Fibrillation Patients With or Without Hypertension: The Fushimi Af Registry
Authors: Tezuka Yuji , DOI KOSUKE , Hamatani Yasuhiro , Ishii Mitsuru , Iguchi Moritake , Masunaga Nobutoyo , Esato Masahiro , Wada Hiromichi , Hasegawa Koji , Ogawa Hisashi , Abe Mitsuru , Akao Masaharu
Published: June 2023

Introduction:
Hypertension (HT) is the main cause of atrial fibrillation (AF) and left ventricular (LV) hypertrophy. Meanwhile, LV hypertrophy can be also the manifestation of some cardiomyopathies. We reported that increased LV relative wall thickness (RWT) was associated with the incidence of thromboembolism events (TE) in patients with non-valvular AF (NVAF). We investigated the association of RWT with TEs in NVAF patients with or without HT.

Methods:
In the Fushimi AF Registry, follow-up data were available for 4,489 patients. Of them, RWT values at enrollment were available for 3,408 patients with NVAF (with HT: n=2,159, without HT: n=1,249). We investigated the relationship between each RWT quartile and the incidence of TEs.

Results:
During the median follow-up period of 1,838 days, 297 TEs occurred. Regardless of the coexistence of HT, higher RWT groups had higher CHA
2
DS
2
-VASc score and higher HELT-E
2
S
2
score and the prescription of oral anticoagulants were comparable among the four groups. The incidence of TEs according to the groups stratified by each RWT quartile with or without HT is shown (Figure). In the multivariate analysis, higher RWT was independent predictors of TEs in the patients with or without HT (Table). The incidence rate of TEs were comparable between RWT>0.6 patients with HT and without HT (2.11 vs. 2.73% per patient-year, log-rank; p=0.67), whereas the patients with HT had higher CHA
2
DS
2
-VASc and HELT-E
2
S
2
scores.

Conclusions:
RWT was independently associated with the incidence of TEs among Japanese patients with NVAF regardless of the concomitance of HT.
Abstract 10748: Development and Internal Validation of the Coronary Revascularization-Tool for Evidence-Based Individualized Share Decision-Making (CR-DECIDE) Major Adverse Cardiovascular Events Model
Authors: Turgeon Ricky D , Lee May , Norris Colleen M , Spertus John , Humphries Karin
Published: June 2023

Introduction:
Coronary revascularization guidelines emphasize shared decision-making (SDM) for chronic CAD management. Decision aids that provide individualized estimates of benefits & risks could improve the relevance & evidence base of SDM. This study sought to develop & internally validate a clinical prediction model for 3-year MACE (death/MI/stroke) in patients with chronic CAD for integration into a point-of-care decision aid.

Methods:
We used the prospective Cardiac Services British Columbia Registry to assemble a cohort of adults with stable angina & obstructive CAD who underwent first diagnostic coronary angiography between 2004-2015, excluding left main disease, LVEF <30%, prior MI/PCI/CABG, NYHA 3-4, & CCS class 4 angina for model derivation. Internal validation was performed with 200 bootstrap samples & missing data was handled by multiple imputation. We included 22 candidate variables with 1 interaction term, based on prior literature, in a Cox proportional-hazards model. We assessed model discrimination & calibration using Harrell’s c-index & the calibration slope, respectively.

Results:
We included 24,990 participants (2026 events). We kept 22 predictors in the final model; the interaction term was removed since it was not significant (p=0.46). Due to non-proportionality, pLAD stenosis & angiographer’s recommended treatment were used as stratification variables (6 strata). Optimism-corrected c-index was 0.69 & calibration slope was 0.97.

Conclusions:
The CR-DECIDE model had moderate ability to predict MACE in patients with chronic CAD, & warrants further validation in an external dataset & impact analysis as part of a point-of-care decision aid.
Abstract 10753: Phosphodiesterase Type 5 Inhibition and C-c Chemokine Receptor-2 Disruption Synergistically Protect Against Pulmonary Arterial Hypertension in Monocrotaline-Treated Rats: Potential Synergism of Anti-inflammatory Agents and Pulmonary Vasodilator Therapy
Authors: TSUBOYA NAOKI , Mitani Yoshihide , Sawada Hirofumi , Oshita Hironori , Ohya Kazunobu , Yodoya Noriko , Ohashi Hiroyuki , Maruyama Kazuo , Hirayama Masahiro
Published: June 2023

BACKGROUND:
Whether conventional pulmonary vasodilator therapy and anti-inflammatory agents synergistically protect against pulmonary arterial hypertension (PAH) is unknown.

Hypothesis:
We tested the hypothesis that a phosphodiesterase type 5 (PDE5) inhibitor and disruption of C-C chemokine receptor (CCR)-2, a receptor for MCP-1, synergistically protect against PAH in monocrotaline (MCT)-treated rats.

Methods:
Study1:Seven-week-old male
Ccr2
(-/-) rats, generated by using the CRISPAR/
Cas9
genome editing technology, or wild-type littermates, treated with MCT (60mg/kg) or vehicle, were subjected to hemodynamic, morphometric and immunohistochemical analyses and mRNA and protein expression studies on day21 (n=40, 4 groups). Study 2: Tadarafil (10mg/kg/d), a PDE5 inhibitor, or vehicle was administered in
Ccr2
(-/-) or wild-type MCT rats on days 21-42 (n=71, 4 groups) for evaluating survival and were evaluated hemodynamically on day28.

Results:
Study1: MCT treatment increased right ventricular systolic pressure (RVSP), an index of right ventricular hypertrophy (Fulton index), indices of pulmonary vascular diseases (%medial wall thickness, %muscularization) and the number of perivascular CD68-positive macrophages in WT rats, all of which were decreased by
Ccr2
(-/-) (p<.05). Similarly, an increase in mRNA expression of inflammatory cytokines (IL6 ,TNFa, MCP1, IL1b, TGFb) and a decrease in BMPR2 pathways (BMPR2, pSmad1/5/9 and ID1) as well as an increase in endothelial apoptosis (% cleaved Caspase 3 positive CD31 cells) and a decrease in NO pathways (eNOS and phospho-eNOS/eNOS) in lungs in wild-type MCT rats were reversed by
Ccr2
(-/-) on day21 (p<.05) with comparable PDE5 expression. Study2: Tadarafil administration or CCR2(-/-)(p=.03 and p=.02) alone improved the survival in wild type MCT rats. A double intervention synergistically improved the survival in separately treated groups (p=.02 vs CCR2(-/-), p=.04 vs Tadarafil) in MCT rats. Tadarafil treatment on days21-28 decreased RVSP and Fulton index in CCR2(-/-) MCT rats (p<.05). Conclusions PDE5 inhibition and CCR-2 disruption synergistically protect against PAH in MCT-treated rats, suggesting an adjunctive role of a CCR2 inhibitor on top of administering a PDE5 inhibitor for PAH.