bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10978: Sleep Duration and Risks of Cardiovascular Disease Onset and Mortality Among Patients With Type 2 Diabetes
Authors: Han Han , Wang Ying , Li Tongtong , Feng Chengwu , Kaliszewski Catherine , Su Yang , Wu Yinfan , Zhou Jian , Wang Liang , Zong Geng
Published: June 2023

Introduction:
Patients with type 2 diabetes (T2D) may have inadequate (insufficient or excessive) sleep which could accelerate CVD onset, but existing evidence from prospective studies is limited.

Hypothesis:
We hypothesized that inadequate sleep duration would be associated with higher risks of CVD incidence and mortality among patients with T2D.

Methods:
This prospective study included 19,345 participants with T2D who were free of CVD and cancer at baseline from the UK Biobank. Sleep duration was obtained at baseline using questionnaires. Cox proportional hazards regression models were used to examine the association of sleep duration with CVD events.

Results:
During an average follow-up of 11.0-12.0 years, we documented 2,219 incident CVD cases (1,555 CADs and 673 strokes) and 652 CVD deaths. Compared with those sleeping for 7-8 h/day, the multivariable-adjusted hazard ratios (95% confidence intervals) of sleeping for ≤5 and ≥10 h/day were 1.39 (1.19-1.61) and 1.38 (1.13-1.68) for incident CVD, 1.26 (1.04-1.51) and 1.23 (0.95-1.57) for CAD, 1.68 (1.30-2.16) and 1.75 (1.27- 2.42) for stroke, and 1.36 (1.02-1.80) and 1.94 (1.42-2.63) for CVD mortality. These results largely remained similar in sensitivity analyses that aimed to address potential reverse causation and in the joint analysis of sleep duration and metabolic control or diabetes severity status.

Conclusions:
Our findings showed inadequate sleep duration was independently associated with increased risks of CVD onset and death among patients with T2D.
Abstract 10986: SGK1 Inhibition Attenuated the Action Potential Duration In-Patient and Genotype-Specific Re-Engineered Heart Cells With Congenital Long QT Syndrome
Authors: Tester David J , Das Saumya , Kim Maengjo , Pradhananga Sabindra , Hamrick Samantha K , Srinivasan Dinesh , Sager Philip , Ackerman Michael J
Published: June 2023

Background:
Long QT syndrome (LQTS) often stems from pathogenic variants in
KCNQ1
(LQT1),
KCNH2
(LQT2), or
SCN5A
(LQT3) and is characterized cellularly by prolongation of the cardiac action potential duration (APD). We have shown that inhibition of serum and glucocorticoid regulated kinase-1 (SGK1) reduces I
NaL
and is proposed as a novel therapeutic strategy for LQT3.

Objective:
To test the efficacy of a potent and selective SGK1 inhibitor (SGK1-I) in human cardiomyocyte models of LQT1, LQT2, and LQT3.

Methods:
Induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) were generated from patients with either LQT1, LQT2, or LQT3. The mexiletine (MEX)-sensitive SCN5A-P1332L iPSC-CMs were tested initially. A CRISPR/Cas9 P1332L variant-corrected isogenic control (IC) was used as a control. The SGK1-I’s therapeutic efficacy was compared to MEX and to a commercially available SGK1 inhibitor (EMD638683). The novel SGK-I was then tested for APD shortening in SCN5A-R1623Q, KCNH2-G604S and KCNQ1-V254M iPSC-CMs. The APD90 values were recorded 4 hours after treatment using FluoVolt.

Results:
The APD90 was significantly prolonged in SCN5A-P1332L iPSC-CMs compared to its IC (646 ± 7 ms vs 482 ± 23 ms, p<0.0001). MEX shortened the average APD90 to 560 ± 7 ms (52% attenuation). Interestingly, SGK1-I significantly shortened the APD to 518 ± 5 ms (78% attenuation) but did not further shorten the APD in the IC. SGK1-I also shortened the APD90 of the SCN5A-R1623Q iPSC-CMs from 753 ± 8 ms to 475 ± 19 ms compared to 558 ± 19 ms with MEX. The SGK1-I shortened the APD90 in KCNH2-G604S (666 ± 10ms to 574 ± 18ms for SGK1-I versus 538 ± 15 ms after MEX). EMD had limited APD shortening effects in SCN5A and KCNH2 iPSC-CMs. Interestingly, while neither MEX nor EMD reduced the APD90 in the KCNQ1-V254M iPSC-CMs, the novel SGK1-I reduced the APD90 from 544 ± 10 ms to 475 ± 11ms (p=0.0004).

Conclusions:
Therapeutically inhibiting SGK1 effectively shortens the cardiomyocyte APD in human heart cell models of the 3 major LQTS genotypes. The novel SGK1-I normalized the pathological APD prolongation almost fully (> 70%) in the patient-derived SCN5A-P1332L iPSC-CM model. These pre-clinical data support further development of SGK1-I as a novel, first-in-class therapy for patients with congenital LQTS.
Abstract 110: Threshold Adjusted Vagus Nerve Stimulation After Asphyxial Cardiac Arrest Results In Reduction Of Endoplasmic Reticulum Stress And Apoptosis
Authors: Choudhary Rishabh C , Ahmed Umair , Shoaib Muhammad , Zanos Stavros , Becker Lance B
Published: June 2023

Background:
Vagus nerve stimulation (VNS) has been shown to improve survival and neurological outcomes after cardiac arrest (CA) and resuscitation by improving mitochondrial function, increasing cerebral blood flow, and reducing inflammation. However, the therapeutic cellular and subcellular mechanisms of VNS are not clearly understood in CA injury. Endoplasmic reticulum (ER) stress after cardiac arrest also contributes to cell death and is an underexplored area.

Objective:
The aim of this study was to investigate the protective effects of customized threshold-adjusted VNS (tVNS) in a rat model of CA and resuscitation in reducing ER stress and cell apoptosis.

Methods and Results:
Sprague-Dawley rats underwent 12 min asphyxial-CA followed by resuscitation. Rats were assigned to either post-resuscitation tVNS for 2 h or no-tVNS (control). tVNS was applied by electrode placement in the left cervical vagus nerve immediately after resuscitation. The tVNS was determined by a 15-20% reduction from the immediate baseline heart rate as the effective and physiological threshold for each animal. This enabled customized parameters for individual animals. At 2 h post-ROSC, rats were perfused with normal saline, and the whole brain was removed. The whole brain was then processed for protein expression by western blotting. We also prepared sham rats that did not receive CA or tVNS. For measuring ER stress we evaluated the expression of p-IRE1α protein and for apoptosis, we measured p-BAD protein. We observed a significantly higher protein expression of p-IRE1α in whole brain tissue after CA in control groups in comparison to the sham (p<0.05). Applying tVNS significantly reduced the expression of brain p-IRE1α in comparison to the control group (p<0.05). CA also substantially increased de-phosphorylation of p-BAD protein compared to the sham group (p<0.05). By contrast, no significant increase in de-phosphorylation of p-BAD protein was observed between the tVNS and sham groups.

Conclusions:
Application of tVNS immediately after 12 minutes of CA and resuscitation results in reduced ER stress and apoptosis. This data suggests that the protective mechanism of tVNS on cell apoptosis involves a reduction in ER stress. tVNS may be a novel therapeutic approach in CA.
Abstract 11024: 3D Localization of Left Bundle Branch Area and Pacing Lead Orientation During Left Bundle Pacing
Authors: Ali Mahmoud , Kieu Andy , Ajam Tarek , Premjee Mohammed , Erickson Lynn , Niazi Imran
Published: June 2023

Introduction:
Left bundle branch area (LBBA) pacing is a novel physiologic pacing technique where the pacing lead is inserted through the right ventricular (RV) septum to capture the LBBA. Among the challenges encountered are identifying the RV septal site, assessing the plane of the lead, determining the depth of insertion, and repositioning the lead to a new site if needed. Navik 3D is a unique localization system that can convert 2D fluoroscopy images into 3D.

Methods:
Following consent, we studied six consecutive patients with a mean age of 72 years who underwent LBBA pacing. Patient characteristics including female sex (n=2), mean body mass index (33.8 kg/m
2
), mean left ventricle ejection fraction (51%), mean intraventricular diastolic thickness (1.06 cm), and presence of hypertension (n=4), diabetes (n=4) atrial fibrillation (n=4), and left bundle branch block (n=1). Patients presented with either complete heart block (n=4) or sinus node dysfunction (n=2). LBBA was localized on the RV septum using fluoroscopy and contrast injection. The RV septum, RV apex, lead position, and His locations were identified in 3D using 2D fluoroscopy from two different views. Then, 3D locations were projected on the 2D fluoroscopy image via the Navik 3D mapping system. The system could also mark an unsuccessful site and allow repositioning.

Results:
All patients had a successful placement in the LBBA with qR in V1, short mean left ventricular activation time (ms) in V6 (73.1), and left bundle potential was recorded in 3 patients.

Conclusions:
Localization of LBBA in 3D is feasible and may be useful for optimal lead placement.
Abstract 11061: Incidence of Cancer in Hospitalized Adults With Congenital Heart Disease
Authors: Caryl Natalie E , June Ciara , Culbert Hunter , Hellinger Riley , Hoyer Andrew , Klewer Scott E , Seckeler Michael D
Published: June 2023

Introduction:
Many patients with congenital heart disease (CHD) are repeatedly exposed to low-dose ionizing radiation for diagnosis, treatment and long-term management of their care.

Hypothesis:
We hypothesized that these repeated exposures put CHD patients at higher risk for radiation-associated cancers (RAC).

Methods:
Review of Vizient (a national, administrative database) from 12/2018 - 12/2021 for admissions aged 18-85 years with ICD-10 codes for moderate or severe CHD and RAC (bladder, breast, colon, esophageal, leukemia/myeloma, liver, lung, ovarian and stomach). Demographics, hospital outcomes and costs were compared to admissions with RAC and no CHD (NO-CHD).

Results:
Out of 34,793 CHD admissions, 6.4% had RAC, and out of 24,999,735 NO-CHD admissions, 11.2% had RAC (p<0.001; Table 1). CHD with RAC were younger, had longer length of stay, higher complications, in-hospital mortality and costs. Comparisons for each RAC type are in Table 2. There were higher rates of breast, liver and lung cancer in CHD (p<0.05 for all) and higher costs for all CHD RAC except esophageal.

Conclusions:
This national database review shows increased incidence of some types of RAC (lung, liver and breast) in adults with CHD, with worse hospital outcomes and higher costs for several cancer types. While frequent radiation in the CHD population may contribute to these findings, it will be important to explore further. These findings also highlight the importance of adherence to the “as low as reasonably achievable” (ALARA) principle in the care of children and adults with CHD and stresses the importance of imaging modalities that do not use ionizing radiation.
Abstract 11064: Role of Renin-Angiotensin System Axis in Human Abdominal Aortic Aneurysm
Authors: Flora Dugaich Vinicius , Mestriner Fabiola , Corsi Carlos , D Avila Mesquita Carolina , Franco Francisco Daniely , Vasconcelos Jociany , Mathias Ferreira dos Santos Cassiana M , Campos Lígia C , Couto Ariel , Jordani Maria CecÃlia C , Joviliano Edwaldo E , Evora Paulo Roberto B , Polonis Katarzyna , Ribeiro Maurício S , Becari Christiane
Published: June 2023

Introduction:
Renin-Angiotensin System (RAS) regulates the cardiovascular system and has been implicated in the development of abdominal aortic aneurysm (AAA). RAS modulates function via balancing the ACE/Chymase/AngII-AT1 receptor and ACE-2/Ang(1-7)-Mas receptor axis. Preferential activation of the ACE/Chymase/AngII-AT1 receptor pathway of the RAS contributes to dysregulation of cardiovascular system and disease while the Ang(1-7)-MasR axis contributes to anti-inflammatory pathways. Therefore, identifying the RAS axis mechanism involved in growth, progression, or the risk of rupture in AAA humans could bring a novel treatment perspective.

Hypothesis:
We hypothesize that in the AAA, the local RAS is altered such as it favours the ACE/AngII/AT1R axis while decreasing the ACE-2/Ang(1-7)/MasR pathway, with consequent AAA development.

Objective:
We sought to investigate the expression of RAS components in the AAA human aorta.

Methods:
Aorta tissue from AAA patients (n=21) was collected during the AAA conventional repair surgery, and aorta control aortas were obtained from organ donors (Control, n=11). Protein expression of renin, chymase, ACE, ACE-2 AT1, AT2, and MAS receptors was analyzed by Western Blotting.

Results:
Our AAA cohort consisted mostly males (76.6% AAA vs. 63.6% Control, p=0.68), smokers or ex-smokers (90.4% AAA vs. 36.3% Control, p=0.002) and most of them had hypertension(71.4% AAA vs. 36.3% Control, p=0.07). Analysis of protein expression in the AAA group showed that ACE and AT1 receptors were upregulated compared with Control (p=0.05; p=0.02, respectively,), while chymase expression was decreased in AAA compared to the control (p=0.03). Additionally, the AAA group showed downregulation in ACE-2 and AT2 compared with Control (respectively, p=0.01, p=0.03). There was no significant difference in the expression of renin and MAS receptors between groups (p=0.52, p=0.41, respectively,).

Conclusions:
Our data show that the ACE/AT1R axis was upregulated while ACE-2 and AT2 receptors were downregulated in the AAA aorta. Our results implicate local RAS in AAA development and warrant further studies.
Abstract 11076: Visualization of Cardiac Uptake of Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicles After Intramyocardial or Intravenous Injection in Murine Myocardial Infarction
Authors: Xu Cynthia M , Sabe Sharif A , Sabra Mohamed , Sellke Frank W , Abid Ruhul
Published: June 2023

Introduction:
In animal models, human bone marrow mesenchymal stem cell-derived extracellular vesicles (MSC-EV) have been found to have beneficial effects in cardiovascular disease, but only when administered via intramyocardial injection. The biodistribution of either intravenous or intramyocardial injection of MSC-EV in the presence of myocardial injury is uncharacterized at this time.

Hypothesis:
Intramyocardial injection will ensure delivery of MSC-EV to the ischemic myocardium, while intravenous injection will not.

Methods:
Human bone marrow mesenchymal stem cells were cultured, and MSC-EV were isolated and characterized. The MSC-EVs were then labeled with DiD lipid dye. FVB mice with normal cardiac function underwent left coronary artery ligation followed by either peri-infarct intramyocardial or tail vein injection of 3*10
6
or 2*10
9
particles of DiD-labeled MSC-EV or a DiD-saline control. The heart, lungs, liver, spleen and kidneys were harvested 2 hours post-injection and were submitted for fluorescent molecular tomography imaging.

Results:
Myocardial uptake of MSC-EV was only visualized after intramyocardial injection of 2*10
9
particles (p = 0.029), and was not detected after tail vein injection of MSC-EV (Figure 1). There were no significantly detectable MSC-EV uptake in other organs after intramyocardial injection, though there was possible focal lung uptake. After tail vein injection of MSC-EV, liver (p = 0.048) and spleen (p = 0.048) appeared to have diffuse MSC-EV uptake.

Conclusions:
Even in the presence of myocardial injury, only intramyocardial but not intravenous administration resulted in detectable levels of MSC-EV in the ischemic myocardium. This study confirms the role for intramyocardial injection in maximal and effective delivery of MSC-EV. Our ongoing studies aimed at developing bioengineered MSC-EV for targeted delivery to the heart may make MSC-EV clinically applicable.
Abstract 11104: Percutaneous Embolization of Extensive Collateral Vessels for Hemoptysis in Pulmonary Aspergilloma
Authors: Ganguly Paulamy , Zhu Zhihao , Lin C Huie
Published: June 2023

Introduction:
Pulmonary aspergillomas form due to fungal colonization in patients with immunocompromise and underlying cavitary lung disease. They can present with hemoptysis due to erosion of pulmonary vessels and formation of collaterals. Arterial embolization of bronchial vessels is considered first line treatment due to effectiveness and minimal invasiveness. We present one patient with need for extensive embolization treatment for persistent hemoptysis.

Case:
53yo woman with pulmonary sarcoidosis and bilateral pulmonary aspergilloma presented to our institution for lung transplant evaluation. She had persistent hemoptysis for years after being diagnosed. She previously had bronchial artery embolization at outside hospital but had persistent symptoms severely limiting her functional status. She continued to have active hemoptysis during the admission, including on arrival to procedure. Angiography demonstrated extensive collateral vessels from systemic arterial to pulmonary circulation including several large branches originating from the subclavian arteries, internal mammary arteries and dorsal scapular arteries. There was leak through multiple previously embolized arteries, with active extravasation of contrast. Initial large collaterals were embolized using Medtronic MVP micro-vascular plugs (3Q, 5Q, 7Q) and smaller collaterals from intercostal arteries embolized using Penumbra Ruby Coil. She had improvement following the first procedure, but had persistent hemoptysis requiring repeat procedures to address more collateral and native vessels prior to resolution of symptoms.

Conclusions:
This patient with bilateral pulmonary aspergilloma had previous unsuccessful coil embolizations and complex collateral vessel system that resulted in severe recurrent bleeds. We successfully treated this patient’s persistent massive hemoptysis after extensive embolizations during multiple challenging procedures.
Abstract 11108: Implementation of High-Sensitivity Cardiac Troponin Assays in the United States: A Report From the NCDR Chest Pain - MI Registry
Authors: McCarthy Cian P , Li Shuang , Wang Tracy Y , Raber Inbar , Sandoval Yader B , Smilowitz Nathaniel R , Wasfy Jason H , Pandey Ambarish , De Lemos James A , Kontos Michael C , Apple Fred S , Daniels Lori B , Newby L Kristin K , Jaffe Allan S , Januzzi James L
Published: June 2023

Introduction:
High-sensitivity cardiac troponin (hs-cTn) assays were first approved for use in the U.S. in 2017. They are the guideline preferred biomarker to evaluate patients with acute chest pain. Few data exist regarding implementation of hs-cTn assays in the U.S.

Hypothesis:
We hypothesize that use of hs-cTn assays has increased over time and that patients assessed with hs-cTn have a shorter length of stay (LOS) and similar use of cardiac testing.

Methods:
We examined trends in implementation of hs-cTn assays among participating hospitals in the NCDR Chest Pain MI Registry from 1/1/2019 through 9/30/2021. Excluding STEMI patients, associations between hs-cTn use, in-hospital diagnostic imaging, and patient outcomes were assessed using logistic or negative binomial regression models.

Results:
Among 550 participating hospitals with 251,000 patients in the registry, implementation of hs-cTn assays increased from 3.3% in Q1, 2019 to 32.6% in Q3, 2021 (P
trend
<0.0001;
Figure
). Implementation was similar by hospital size, type, and geographic location. hs-cTn use was associated with more echocardiography among patients with NSTE-ACS (82% vs. 75%; aOR: 1.43, 95% CI, 1.19-1.73) but not in low-risk chest pain. hs-cTn use was associated with decreased odds of invasive coronary angiography in low-risk patients (3.7% vs. 4.5%; aOR: 0.73, 95% CI, 0.58-0.92) but similar use in NSTE-ACS. There was no association between hs-cTn use and non-invasive stress/CTCA testing. Among NSTE-ACS patients, hs-cTn use was not associated with PCI, CABG, or in-hospital mortality. Use of hs-cTn was associated with shorter LOS (47.6 hours vs. 48 hours; IRR: 0.96, 95% CI, 0.93-0.98).

Conclusions:
Although implementation of hs-cTn among U.S. hospitals is increasing, most U.S hospitals continue to use less-sensitive troponin assays. hs-cTn use was associated with shorter LOS overall, greater use of echocardiography in NSTE-ACS, and lower use of invasive angiograms in low-risk patients.
Abstract 11122: Sex Differences and Disparities in Cardiovascular Outcomes of Covid-19
Authors: Bergami Maria , Cenko Edina , Yoon Jinsung , scarpone marialuisa , Badimon Lina , David Antonio , Demiri Ilir , Maria Dorobantu , Fronea Oana Gheorghe , Jankovic Radmilo , Kedev Sasko , Ladjevic Nebojsa , Lasica Ratko , Loncar Goran , Mancuso Giuseppe , Mendieta Badimon Guiomar , Passalic Marijan , Mjehovic Petra , Milicic Davor , Petrovic Milovan , Poposka Lidija , Stefanovic Milena , van der Schaar Mihaela , Vasiljevic Zorana , vavlukis Marija , Vega Pittao Maria Laura , Vukomanovic Vladan , Zdravkovic Marija , Nava Stefano , Caramori Gaetano , Manfrini Olivia , Bugiardini Raffaele
Published: June 2023

Introduction:
Previous analyses on sex differences in case-fatality rates at population-level data had limited adjustment for key patient clinical characteristics thought to be associated with COVID-19 outcomes.

Hypothesis:
We aimed to estimate the risk of specific organ dysfunctions and mortality in women and men.

Methods:
This retrospective cross-sectional study included 17 hospitals within 5 European countries participating in the International Survey of Acute Coronavirus Syndromes (ISACS) COVID-19 (NCT05188612). Participants were individuals hospitalized with positive SARS-CoV-2 from March 2020 to February 2022. Risk-adjusted ratios (RR) of in-hospital mortality, acute respiratory failure (ARF), acute heart failure (AHF), and acute kidney injury (AKI) were calculated for women versus men. Estimates were evaluated by inverse probability of weighting and logistic regression models

Results:
The overall care cohort included 4,499 patients with COVID-19 associated hospitalizations. Of these, 1,524 (33.9%) were admitted to ICU, and 1,117 (24.8%) died during hospitalization. Compared with men, women were less likely to be admitted to ICU (RR: 0.80; 95%CI: 0.71-0.91). In general wards and ICU cohorts, the adjusted women-to-men RRs for in-hospital mortality were of 1.13 (95%CI: 0.90-1.42) and 0.86 (95%CI: 0.70-1.05; p
interaction
=0.04). Development of AHF, AKI, and ARF was associated with increased mortality risk (OR: 2.27; 95%CI; 1.73-2.98, OR: 3.85; 95%CI: 3.21-4.63 and OR: 3.95; 95%CI: 3.04-5.14, respectively). The adjusted RRs for AKI and ARF were comparable among women and men regardless of intensity of care. By contrast, female sex was associated with higher odds for AHF in general wards, but not in ICU (RRs: 1.25;9 5%CI: 0.94-1.67 versus 0.83; 95%CI: 0.59-1.16, p
interaction
=0.04).

Conclusions:
Women in general wards were at increased risk of AHF and in-hospital mortality for COVID-19 compared with men. For patients receiving ICU care, fatal complications including AHF and mortality appeared to be independent of sex. Equitable access to COVID-19 ICU care is needed to minimize the unfavourable outcome of women presenting with COVID-19 related complications.
Abstract 11126: Longitudinal MRI-Based Superficial Femoral Artery Velocity Measurements in Peripheral Artery Disease: An Analysis of the Effect of Lipid Modification on Peripheral Artery Disease After Endovascular Intervention Trial (ELIMIT)
Authors: Sinharoy Ankita , Reddy Neeti , Lin John K , NAMBI VIJAY , Yang Eric Y , Kougias Panagiotis , Taylor Addison A , Lumsden Alan , Ballantyne Christie M , Brunner Gerd
Published: June 2023

Introduction:
Peripheral artery disease (PAD) causes lower extremity dysfunction and is associated with an increased risk of cardiovascular mortality and morbidity. We analyzed longitudinal associations of non-invasive 2-dimensional-phase-contrast magnetic resonance imaging (2D-PC-MRI) velocity markers of the distal superficial femoral artery (SFA) with characteristics of PAD.

Hypothesis:
Longitudinal changes in MRI-based measures of SFA velocity are associated with changes in SFA lumen volumes in PAD.

Methods:
A total of 33 (11 diabetic, 22 non-diabetic) PAD patients, who completed baseline and 2-year follow-up MRI were included in this secondary analysis of ELIMIT. Electrocardiographically-gated 2D-PC-MRI was performed at a proximal and a distal imaging location of the distal SFA territory. SFA lumen, wall, and total vessel volumes were averaged over all distal SFA MRI slices.

Results:
Baseline characteristics did not differ between diabetic and non-diabetic PAD patients (Table). Proximal and distal SFA velocity measures did not differ between baseline and 2-years (41.98: IQR (23.58, 72.6) cm/s; vs. 40.31: IQR (26.69, 61.29) cm/s; p=0.30, for maximum SFA velocity). The velocity amplitude (defined as the difference between the SFA minimum and maximum velocity) was significantly lower in the distal compared to the proximal SFA location at both baseline and at the 2-year visit (p=0.003, p<0.001). In a pooled analysis of all 33 PAD patients, the 2-year change of the average SFA

velocity was significantly associated with the 2-year change in the averaged SFA lumen volume (beta: 0.00011, r
2
: 0.175, p=0.017). In a subgroup analysis, a similar pattern was observed in diabetic patients (beta: 0.00006, r
2
: 0.714, p=0.001), but not in non-diabetics (beta: -0.000019, r
2
: 0.0095, p=0.68).

Conclusion:
Longitudinal 2D-PC-MRI SFA velocity changes are associated with 2-year SFA lumen changes. 2D-PC-MRI velocity measures may be of interest in assessing PAD.
Abstract 11130: Impact of Metabolic Surgery on Left Ventricular Structure and Function in Patients at High Risk for Heart Failure With Preserved Ejection Fraction
Authors: Hughes Diarmaid , Sanaka Krishna , Wilson Rickesha , Saijo Yoshihito , Chan Nicholas , Kumar Ashwin , Grimm Richard A , Griffin Brian P , Tang Wai Hong , Nissen Steven E , Aminian Ali , Xu Bo
Published: June 2023

Introduction:
Obesity is a major risk factor for HFpEF. Metabolic surgery has proven to be effective in reducing heart failure incidence.

Hypothesis:
This study examined the impact of metabolic surgery on LV structure and function in patients with high risk for HFpEF.

Methods:
Patients undergoing metabolic surgery between March 2005 and February 2019 with pre- and post-operative TTE imaging, a preserved EF (>=50%) and a H
2
FPEF score >=5 were recruited for this study. A H
2
FPEF score of ≥5 is considered a high possibility of HFpEF diagnosis.

Results:
Table 1 shows baseline characteristics of the 126 patients that met the entry requirements. The mean age was 65.5 years (SD 8.9) and 64.3% were female. Table 2 outlines the clinical and echocardiographic variables before and after metabolic surgery. There was a significant decrease in mean body mass index (BMI) post operatively, from 47.7 to 36.6 (P<0.001), along with a number of statistically significant improvements in cardiovascular risk factors including a decrease in mean systolic blood pressure (BP) from 138 to 131 mmHg (P=0.005) and mean diastolic BP from 75 to 71 mmHg (P=0.014). There were improvements seen in the LV structure and function with the LV mass decreasing from 247.8 g to 220.7 g (P<0.001), and both the mean septal wall (1.4 cm to 1.3cm, P<0.001) and posterior wall (1.2 cm to 1.1 cm, P=0.007) thicknesses decreasing. There was also an improvement in the average LV global longitudinal strain (GLS) from -15.6 to -17.7% (P<0.001).

Conclusions:
This study demonstrates that for patients at high risk of HFPEF, metabolic surgery was associated with improvements in LV structure and function, including LVGLS.
Abstract 11135: Association of Digoxin Use With Transplant-Free Survival in Infants Palliated With a Stage I Hybrid Procedure
Authors: Reddy Reshma K , Zyblewski Sinai C , Chowdhury Shahryar M , Godown Justin , Bradley Scott M , Duncan Rachel K , Brown David W , Brown Tyler N , Bates Katherine E , Minich Luann , Costello John M
Published: June 2023

Introduction:
Digoxin use in patients with single ventricle physiology after stage I palliation (S1P) has been associated with reduced interstage mortality (IM). However, the S1P hybrid procedure comprised a small fraction of the patients in these evaluations. As it is being performed with increasing frequency, data regarding digoxin effects on IM after this procedure are needed. We sought to determine if digoxin prescription at discharge in infants with the S1P hybrid was associated with improved transplant-free interstage survival.

Methods:
National Pediatric Cardiology Quality Improvement Collaborative registry data from 2008 to 2021 were utilized. Infants discharged home after the S1P hybrid hospitalization were included. Patients were excluded if they had 1) supraventricular tachycardia, 2) death during S1P hospitalization, 3) conversion to Norwood during S1P hospitalization, or 4) remained hospitalized until stage II surgery. The primary outcome was transplant-free survival. Chi-square, Fisher’s Exact, Mann-Whitney U tests and multivariable logistic regression were used to compare patients receiving and not receiving interstage digoxin following S1P hybrid.

Results:
Of the 259 patients from 45 sites with S1P hybrid, 129 (50%) were discharged home on digoxin. Baseline characteristics including birth weight, gestational age at birth, race/ethnicity, cardiac diagnosis, presence of aortic atresia, noncardiac abnormalities or genetic syndromes, and one or more pre-operative risk factors were similar between groups. IM or heart transplant occurred in 30 (23%) patients in the no digoxin group compared to 18 (14%) in the digoxin group (P=0.06). With multivariate logistic regression analysis adjusting for home feeding route, degree of right ventricular dysfunction, atrioventricular valve regurgitation and oxygen saturation at discharge, home digoxin prescription was independently associated with a lower risk of IM or transplant (adjusted OR 0.49; 95% CI 0.25-0.98; P=0.04).

Conclusions:
In patients with single ventricle physiology who underwent a S1P hybrid procedure, digoxin prescription at hospital discharge was associated with improved transplant-free survival during the interstage period.
Abstract 11145: Biomechanical Engineering Analysis of Leaflet Kinematics and Native Coronary Flow After Valve-Sparing Aortic Root Replacement Using Four Graft Configurations
Authors: Zhu Yuanjia , Pandya Pearly K , Park Matthew H , Mullis Danielle , Wilkerson Robert , Baraka Abakar , Stark Charles J , Wu Catherine A , Joo Hyunchel , Woo Y. Joseph J
Published: June 2023

Introduction:
Different ex vivo root biomechanics after valve-sparing aortic root replacement (VSARR) using several graft configurations have been described. The impact of graft choice on each cusp’s kinematics and native coronary flow remains unclear. The objective was to analyze valve kinematics and coronary flow after VSARR using 4 graft configurations in a 3D-printed heart simulator (
Fig A
).[YZ1]

Methods:
Porcine aortic roots with coronary arteries were explanted (n = 5). Native roots served as controls (
Fig B
). Each sample underwent VSARR using straight graft (SG), Valsalva graft (VG), anti-commissural plication (ACP), and Stanford modification (SMOD) in a random order (
Fig C-G
). Hemodynamics and videometric data were analyzed (
Fig H, I
).

Results:
SG showed the lowest regurgitant fraction (2.8 ± 1.5 %) compared to control (6.3 ± 3.9 %,
p
= .0002), VG (12.2 ± 3.6 %, p = .002), ACP (12.9 ± 1.3 %,
p
= .001), and SMOD (12.2 ± 3.0 %,
p
= .001,
Fig J, K
). The left coronary artery flow was higher in SG (0.68 ± 0.16 L/min) compared to VG (0.55 ± 0.22 L/min,
p
= 0.05) and SMOD (0.51 ± 0.23 L/min,
p
= 0.05,
Fig L
). The right coronary artery flow was higher in SG (0.20 ± 0.10 L/min) compared to VG (0.07 ± 0.04 L/min,
p
= 0.04) and SMOD (0.08 ± 0.05 L/min,
p
= 0.04,
Fig M
). SG (26.5 ± 17.6 cm/s) compared to VG (48.3 ± 19.0 cm/s,
p
= .001) and SMOD (39.5 ± 10.1 cm/s,
p
= .05) showed lower rapid opening velocity in the left coronary cusp (LCC). SG (8.1 ± 6.2 cm/s) compared to VG (15.0 ± 10.6 cm/s,
p
= .04) showed lower rapid closing velocity in the right coronary cusp. The VG (17.7 ± 9.7 Hz) had higher flutter frequency in the LCC compared to control (11.9 ± 4.1 Hz,
p
= .02). The SG (11.9 ± 4.5 dB/Hz) compared to ACP (16.4 ± 4.7 dB/Hz,
p
= .01) showed lower flutter power in the LCC.

Conclusions:
Compared to other configurations, SG had the most optimal hemodynamics, native coronary flow, and leaflet kinematics. Further in vivo validation studies should be performed to evaluate flow dynamics in the root and assess for clinical applicability.
Abstract 11148: Time-Varying Cardiovascular Effects of Sodium-Glucose Co-Transporter Inhibitors in Patients With Type 2 Diabetes: Insights From Pivotal Cardiovascular Outcome Trials
Authors: Milioglou Ioannis , Motairek Issam , Deo Salil , Neeland Ian , Rajagopalan sanjay , Al-Kindi Sadeer
Published: June 2023

Introduction:
Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have been shown to reduce cardiovascular (CV) risk in patients with type 2 diabetes. Trial results reported as hazard ratios (HR) may be of limited use in shared decision-making. Restricted mean survival time (RMST) is an alternative reported in time units and can be easily interpreted.

Hypothesis:
We sought to investigate the effects of SGLT2i on CV outcomes using RMST in pivotal trials in patients with type 2 diabetes.

Methods:
Data from 5 trials of SGLT2i (CANVAS, CREDENCE, EMPAREG-OUTCOME, DECLARE-TIMI 58, VERTIS CV) for the following end-points: major adverse cardiovascular events (MACE: myocardial infarction, stroke, and cardiovascular death), heart failure hospitalizations (HFH), cardiovascular death and all-cause mortality was extracted from the Kaplan Meier curves. For each trial, we calculated the RMST difference (ΔRMSTs) between SGLT2i and placebo arms, which were then pooled using random effect models. Results for all trials were extrapolated till 7 years (CANVAS trial maximum follow-up), when necessary, using flexible parametric model

Results:
Four trials were included for MACE (CANVAS, EMPAREG OUTCOME, VERTIS CV, DECLARE TIMI 58). dRMST for MACE increased non-linearly over time from year 1 (1.2 [0.2-2.2] days) to year 7 (19.5 [5.3-33.8] days). For HFH (CANVAS, EMPAREG OUTCOME, VERTIS CV), dRMST increased non-linearly from year 1 (1.2 [0.7-1.7] days) to year 7 (26.3 [15.2-37.3] days), Figure. For CV death (CANVAS, CREDENCE, EMPAREG OUTCOME, VERTIS CV), dRMST increased non-linearly from year 1 (0.6 [0.2-1.1] days) to year 7 (34.8 [3.3-66.4] days). For all-cause mortality (CANVAS, CREDENCE, EMPAREG OUTCOME, DECLARE-TIMI 58), dRMST increased non-linearly from year 1 (0.2 [-0.1-0.6] days) to year 7 (39.1 [2.8-75.5] days).

Conclusions:
SGLT2i are associated with a statistically significant, time-dependent, non-linear delay in MACE, HFH, cardiovascular and all-cause deaths.
Abstract 11157: A Rare Case of Concomitant Dual Genetic Cardiomyopathies in a Patient Complicated by Stroke
Authors: Ranasinghe Mark P , Kwok Cecilia , Lim Han , Bodek Simon , Nolan Mark
Published: June 2023

Background:
Very little evidence exists on the prevalence of co-existing cardiomyopathies. We report in this case a highly atypical presentation of concurrent arrhythmogenic right ventricular cardiomyopathy (ARVC) and hypertrophic cardiomyopathy (HCM) likely attributable to simultaneous separate somatic mutations, complicated by stroke.

Case:
A 60-year-old male with a history of rheumatoid arthritis, sleep apnoea and obesity with no significant coronary disease referred for review of asymptomatic ECG abnormalities was found to have severe asymmetrical left ventricular (LV) wall thickening with apical segment akinesis and an LV apex mass on echocardiogram. She had a family history of early sudden cardiac death, with an otherwise unremarkable history and physical examination.

Clinical Course:
Cardiac MRI (CMR) subsequently demonstrated aneurysmal dilatation of LV apical segments with a 17x13mm thrombus present. Systolic anterior mitral leaflet motion was seen, and a dilated right ventricle (RV) with 240ml end-diastolic volume and 27% ejection fraction. "Accordion" sign was present in the sub-tricuspid RV free wall with dyskinesia, and ECGs confirmed presence of epsilon waves. One week after CMR, she suffered a large left middle cerebral artery (MCA) stroke in the setting of warfarin cessation due to echocardiography-suggestive absence of thrombus.

Discussion:
Genetic analysis revealed a mutated Plakophillin 2 (PKP2) gene, and FHOD3 gene associated with HCM of uncertain significance. The diagnosis was concomitant genetic cardiomyopathies of ARVC and HCM complicated by large LV apical aneurysm and thrombus culminating in left MCA stroke. PKP2 mutations to date have not been associated with hypertrophic phenotypes. This case therefore demonstrates the unlikely 1 in 2,500 incidence of coexistence of two separate cardiomyopathies likely attributable to simultaneous separate somatic mutations, while also highlighting the central role of CMR in investigation and diagnosis of RV pathology. In addition to this case, prior studies have also shown echocardiography can only identify 50% of ARVC cases identified by CMR, suggesting that selective use of CMR may double the number of identified cases of this life-threatening disease.
Abstract 11159: Assessment of Atrial Cardiomyopathy by High-Density Mapping Can Guide Additional Procedures in AF Ablation
Authors: Han Seongwook , Hwang Jongmin , park Hyoung-Seob
Published: June 2023

Background:
The efficacy of catheter ablation (CA) for atrial fibrillation (AF) has been lower in persistent AF (PeAF). Additional ablation strategies beyond pulmonary vein isolation (PVI) are not routinely recommended in PeAF because their efficacy is not established yet. The clinical AF patterns could not expect the degree of atrial abnormal voltage area (AVA). The inability to discriminate significant atrial cardiomyopathy may lead to diverse ablation outcomes beyond PVI in PeAF.
Objectives:
The objective of this study was to find out how much proportion of AVA can predict higher AF recurrence after PVI.

Methods:
We enrolled the consecutive 49 patients who underwent CA of AF. LA was mapped with Pentaray® catheter (2-6-2 spacing) during mid-CS pacing (600msec) using the CONFIDENCE Module. The peak-to-peak bipolar voltage was obtained using only 2mm spacing electrodes. The AVA was defined when the bipolar voltage was < 1.5mV, which is known to be normal in LA. After excluding PVs, appendage, and mitral valve region, the proportion of AVA was calculated by the Carto 3 mapping system. The ablation strategy was PVI only regardless of the AF pattern & degree of AVA.

Results:
The mean age was 58.1 ± 7.7 years, and 73.5% were male. The average mapping points were 3557.5 ± 760.9. The average proportion of AVA was 31.4 ± 15.3%. The paroxysmal AF (PAF) patients were 71.4%, and the mean AVA between PAF and PeAF was significantly different (28.7 ± 15.5 vs. 38.2 ± 12.7, p=0.049). The mean follow-up duration was 265.8 ± 150.4 days. Atrial tachyarrhythmia recurred in 35.7%. In receiver-operating curve analysis, the proportion of AVA of 33.4% predicts AF recurrence regardless of AF type with a sensitivity of 75% and specificity of 78.8% (AUC 0.864, P<0.001).

Conclusion:
More than one-third of AVA assessed by high-density mapping could be used as a predictor of the recurrence of AF after CA, which may guide the consideration of additional ablation. However, a randomized controlled trial is warranted.
Abstract 11164: Precise Genomic Correction of
RBM20
Mutations Rescues Dilated Cardiomyopathy
Authors: Nishiyama Takahiko , Zhang Yu , mcanally john , Xu Lin , Liu Ning , Bassel-duby Rhonda S , Olson Eric N
Published: June 2023

Introduction:
Despite current medical advancements, effective treatment for familial cardiomyopathies remains challenging. Mutations in RNA binding motif protein 20 (
RBM20
) are a common cause of dilated cardiomyopathy (DCM). Many
RBM20
mutations cluster within the arginine/serine rich (RS-rich) domain, which mediates nuclear localization. These mutations induce RBM20 mis-localization and abnormal alternative splicing of cardiac genes. Importantly, the formation of aberrant ribonucleoprotein (RNP) granules in the cytoplasm of cardiomyocytes may contribute to DCM.

Hypothesis:
Precise genomic editing using base editing (BE) or prime editing (PE) corrects the mutations and rescues the pathophysiology of RBM20-related DCM.

Methods:
We used adenine base editing (ABE) or PE to correct the pathogenic p.R634Q (c.1901 G>A) and p.R636S (c.1906 C>A) mutations in the RS-rich domain of
RBM20
in human isogenic induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM). Additionally, using a humanized
Rbm20
mutant mouse (R636Q/R636Q), we assessed in vivo ABE correction for DCM treatment.

Results:
Correcting
RBM20
R634Q
human iPSC by ABE using ABEmax-VRQR-SpCas9 and sgRNA components, we showed 89% efficiency of A to G editing, recovery of alternative splicing of cardiac genes, restoration of nuclear localization of RBM20 and elimination of RNP granule formation. Additionally, we developed a PE strategy to correct the
RBM20
R636S
mutation in iPSCs and observed A to C editing at 40% efficiency. To evaluate the potential of ABE for DCM treatment, we systemically delivered ABE components by adeno-associated virus in postnatal
Rbm20
mutant mice (R636Q/R636Q). Uncorrected R636Q/R636Q mice exhibited severe heart failure and premature death by 3-months of age. In contrast, R636Q/R636Q mice receiving systemic ABE components showed a substantial improvement of LV function and an increase in life span. As seen by RNA-seq analysis, ABE correction rescued the transcriptional profile of treated R636Q/R636Q mice, while untreated mice showed altered cardiac gene expression.

Conclusions:
Precise gene editing technologies provide an innovative approach to correct disease-causing genomic mutations in cardiovascular diseases.
Abstract 11174: Hypertension in Hispanics/Latinos is Associated with Adverse Alterations in Cardiac Structure and Function
Authors: Nguyen Nga , Nosair Waseem , Claggett Brian , Pabon Maria , Rodriguez Carlos J , Solomon Scott , Cheng Susan , Chandra Alvin
Published: June 2023

Introduction:
Hispanic/Latino adults have been reported to be less aware of their hypertension (HTN) diagnosis and less likely to be on treatment compared to non-Hispanic white and black adults. These disparities suggest that Hispanic adults with HTN are at high risk for developing structural heart disease. Yet, limited data exist regarding how HTN affects cardiac structure and function in this population.

Hypothesis:
Higher long-term antecedent blood pressure (BP) level is associated with adverse changes in cardiac structure and function in Hispanic/Latino adults.

Methods:
The study sample consisted of 6,144 participants of the Hispanic Community Health Study/Study of Latinos free of prior cardiovascular disease who had BP measured at visits 1 and 2 (2010-2011 and 2014-2017, respectively) and underwent echocardiography at visit 2. Mean systolic and diastolic BP were averaged across visits 1 and 2. Those who were taking antihypertensive medications were imputed as follows: values for systolic BP (+10 mmHg) and diastolic BP (+5 mmHg).

Results:
Mean age was 57±10 years, 54% were women. 48% had imputed mean systolic BP ≥130 or diastolic BP ≥80 mmHg. Increasing age, body mass index (BMI), diabetes prevalence, and worsening kidney function were associated with more severe hypertension. Increasing mean BP was associated with increased prevalence of concentric remodeling and concentric left ventricular (LV) hypertrophy. Higher BP was also associated with adverse changes in diastolic function parameters including left atrial volume index, septal e’, E/A ratio, and E/e’. These differences persisted after adjusting for age, sex, Hispanic subgroup, BMI, kidney function, diabetes, alcohol use, and cholesterol level. LV ejection fraction did not significantly differ across BP groups.

Conclusions:
Increased prevalence of HTN in a Hispanic/Latino adult population is associated with LV hypertrophy, concentric remodeling, and diastolic dysfunction.
Abstract 11187: Impact of Hypertriglyceridemia on Cardiovascular Mortality According to Low-Density Lipoprotein Cholesterol in a 15.6-Million Population
Authors: Park Hyung-Bok , Arsanjani Reza , Hong Sung-jin
Published: June 2023

Introduction:
The role of hypertriglyceridemia (HTG) in cardiovascular disease (CVD) remains controversial, especially in persons with well-controlled low-density lipoprotein cholesterol (LDL-C).

Hypothesis:
We aimed to evaluate the association between triglyceride (TG) levels and CVD mortality according to LDL-C and age in a general population.

Methods:
From the Korean National Health Insurance Service database, 15,672,028 participants aged 18-99 who underwent routine health examinations were followed up for CVD mortality. Hazard ratios (HRs) for CVD mortality were calculated using Cox models after adjusting for various confounders.

Results:
During a mean 8.8 years of follow-up, 105,174 individuals died from CVD. There was a clear log-linear association between TG and overall CVD mortality down to 50 mg/dL. Each two-fold increase in TG was associated with 1.10-fold (overall CVD), 1.22-fold (ischemic heart disease [IHD]), 1.24-fold (acute myocardial infarction [AMI]), and 1.10-fold (ischemic stroke) higher CVD mortality. Hemorrhagic stroke and heart failure were not associated with TG levels. The impact of HTG on CVD weakened but remained present in persons with LDL-C <100 mg/dL, in whom each two-fold higher TG was associated with 1.05-fold (overall CVD), 1.12-fold (IHD), 1.15-fold (AMI), and 1.05-fold (ischemic stroke) higher CVD mortality. The younger population (18 to 44 years) had stronger associations between TG levels and mortality from overall CVD, IHD, and AMI than the older population.

Conclusions:
HTG independently increases CVD mortality. There are residual risks of HTG in both young and older individuals with a low level of LDL-C. HTG management might be beneficial in individuals with well-controlled LDL-C.
Abstract 11216: Greater Prognostic Value of Left Atrial Mechanics Compared to Left Atrial Volume in Atrial Functional Mitral Regurgitation
Authors: Cramariuc Dana , Alfraidi Hassan , Nagata Yasufumi , Levine Robert , Andrews Carl , Hung Judy
Published: June 2023

Introduction:
Atrial functional mitral regurgitation (AFMR) is associated with increased mortality and morbidity. Optimal management however remains unclear. Mechanism of AFMR is linked to left atrial remodeling yet left atrial (LA) size and function are still poorly characterized.

Objectives:
To assess LA size and function by reservoir strain (LASr) and reservoir work (LAWr) and their impact on outcome in AFMR.

Methods:
Consecutive patients examined at our institution between 2001-2019 and with AFMR of at least moderate MR degree were examined. LAWr was estimated as LASr x LA reservoir volume, and patients were grouped by median LASr or LAWr. Outcomes were all-cause death or heart failure hospitalizations.

Results:
515 patients with moderate or greater AFMR were followed for a median of 5 [range 1-17] years. All patients had previously documented atrial fibrillation (AF) (38%), heart failure with preserved ejection fraction (HFpEF) without AF (24%), or both (HFpEF+AF, 38%). LA volume was largest in AF patients and smallest in HFpEF while LA function parameters were greater in HFpEF and AF compared to the combined HFpEF+AF group (Fig. A,B).During follow-up, patients with low LASr or LAWr had higher risk of death (p <0.001, Fig. C) and heart failure hospitalizations (p<0.05). In Cox regression analyses, low LASr and LAWr, but not LA volume and left ventricular function, were associated with a higher risk of death (LASr: HR 2.3 (95% CI 1.6-3.5); LAWr HR 3.4 (95% CI 2.4-4.7), both p<0.001) after adjustment for clinical and echocardiographic confounders.

Conclusion:
LA reservoir function but not LA size is a robust predictor of outcome in AFMR with moderate or greater MR. This provides mechanistic insights into the interplay of functional parameters versus LA geometric changes in AFMR.