bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12028: Neural Mechanisms of Postoperative Atrial Fibrillation Suppression Using Nanoformulated Calcium Targeting Cardiac Ganglionated Plexi
Authors: Jafree Ehsan , O'Quinn Michael , Myadam Rahul , Rose Brianna , Dormer Kenneth , Nguyen Kytai T , Das Anindita , Quader Mohammed , KASIRAJAN Vigneshwar , Kaszala Karoly , Ellenbogen Kenneth A , Huizar Jose , Tan Alex Y
Published: June 2023

Introduction:
The neural mechanisms of postoperative atrial fibrillation (POAF) remain unclear.

Hypothesis:
We hypothesize that injection of left atrial GP with nanoformulated calcium chloride (nCaCl2) causes GP neuroapoptosis, inhibition of sympathetic and vagal nerve activity (SNA, VNA) and consequent suppression of POAF.

Methods:
In a novel canine model of POAF with serial bilateral thoracotomy surgeries, we assessed ambulatory SNA and VNA before (baseline), 3-days after and 6-weeks after injection of 1ml of nCaCl2 (n=6) or sham (n=3) into each of 4 left atrial GP. We also serially assessed atrial effective refractory period (AERP) and AF vulnerability (AFV) by in-vivo programmed stimulation before and 6 weeks after nCaCl2 treatment.

Results:
In this POAF model, postoperative atrial electrical remodeling manifests as a reduction in AERP and increase in AFV from baseline (week 0) to postop (week 3) (Table). Subsequent nCaCl2 treatment at week 3 reversed these changes (increased AERP, decreased AFV) at 6 weeks post-treatment, vs persistently decreased AERP and increased AFV in the sham control group. Three days after nCaCl2 treatment, there was a reduction in SNA and VNA vs baseline and increase in mean and standard deviation (SD) RR intervals vs baseline, whereas the sham group demonstrated the opposite changes (increased SNA, decreased mean RR and SDRR vs baseline). At 6-weeks post-treatment, mean and SDRR remained persistently increased whereas SNA remained suppressed vs baseline. In contrast, SNA remained elevated and mean RR decreased vs baseline in the sham group. Histology demonstrated neuronal apoptosis within GP without atrial myocardial infiltration in nCaCl2-treated but not in sham.

Conclusions:
Modulation of cardiac GP with nanoformulated calcium causes GP neuroapoptosis, which exerts a persistent sympatho- and parasympatholysis across the cardiac neuraxis, promoting reversed atrial electrical remodeling and durable suppression of POAF.
Abstract 12041: Tyrosine Kinase Inhibitors Leads to Sodium Channel Dysfunction in the Heart
Authors: Greenlee Ashley , Schwendeman Ethan , Scott Shane , Musa Hassan , Stein Matthew , Patel Divya , Mohammad Somayya , Smith Sakima A
Published: June 2023

Tyrosine Kinase Inhibitors (TKIs) are used by tens of thousands of patients and are efficacious for treating renal cell carcinoma . However, TKIs have been reported to have numerous off-target effects, including arrhythmias and heart failure. Many patients who receive TKIs are over 60 years of age and have existing cardiac diseases, thus increasing their risk of cardiotoxicity. However, the exact mechanism to how these TKIs cause cardiotoxicity remains unclear. Our research goal is to understand how TKIs lead to cardiotoxicity by learning what proteins are being targeted and what are potential upstream regulators so we can introduce possible treatments that can combat these effects. Recent literature has stated that the TKI Sorafenib led to increased reactive oxygen species (ROS) production and Calcium (Ca
2+
)/Calmodulin dependent kinase II (CaMKII) activity in rat ventricular cardiomyocytes. ROS can activate CaMKII, and increased CaMKII activity can lead to hyperphosphorylation of the voltage-gated sodium channel, leading to pathophysiological enhancement of late sodium current (I
Na,L
). Increased activity of CaMKII and I
Na,L
can be seen in arrhythmias and heart failure. We hypothesize that TKIs lead to an increase enhancement of I
Na,L
due to an increase in ROS production and increased CaMKII activity. To test this hypothesis, we treated H9c2 myoblasts with Pazopanib (n=3) or DMSO (n=3) and wild-type mice with Pazopanib (n=5) or DMSO (n=5). After treatment, we assessed cytosolic and mitochondrial ROS production
in vitro
and functional affects, CaMKII activity, and I
Na,L
current
in vivo
. Results showed that Pazopanib led to a significant increase in ROS production in H9c2 cells and more arrhythmogenic events in WT mice. While CaMKII activity or I
Na,L
expression was not significantly changed between the two groups, with electrophysiology studies Pazopanib did lead to alterations in amplitude, peak current, ultra-slow inactivation, and recovery. In conclusion, Pazopanib leads to cardiovascular dysfunction and this could be due to an increase in ROS production and altered sodium channels. Our study indicates a potential mechanism as to how TKI treatment leads to cardiotoxicity in patients.
Abstract 12042: A Mouse Model of Heart Failure With Preserved Ejection Fraction Driven by Hyperlipidemia and Enhanced Cardiac LDLR Expression
Authors: Williams Monique M , Condor Capcha Jose Manuel , Iansen Irion Camila , Seo Grace , Lambert Guerline , Kamiar Ali , Kanashiro-Takeuchi Rosemeire M , Takeuchi Lauro , Saad Ali , Mendez Armando J , Webster Keith A , Goldberger Jeffrey J , Hare Joshua M , Shehadeh Lina A
Published: June 2023

Background:
HFpEF prevalence has surpassed that of HFrEF. Elevated accumulation of myocardial lipids is a prominent feature of HFpEF patients and the gene for lipoprotein lipase (LPL) in cardiac biopsies is decreased compared with HFrEF or healthy controls. Poloxamer-407 (p407) induces hyperlipidemia by blocking LPL and increasing plasma triglycerides (TG) and LDL cholesterol. We hypothesized that hyperlipidemia driven by p407 and overexpression (OE) of cardiac LDLR in mice mimics a subset of human HFpEF.

Methods:
WT-129 mice were subject to 4 wks of biweekly i.p. p407-injections with or without a single i.v. injection of AAV9-cTnT-LDLR (n=31); AAV9-cTnT-Luciferase control (n=11), or single i.v. injection with AAV9-cTnT-LDLR alone (n=10). Treatment groups were compared to an untreated group (n=26). Echo, blood pressure (BP), whole-body plethysmography (WBP), ECG telemetry, activity wheel monitoring (AWM), biochemical tests, and histological changes were assessed at 4-8 wks.

Results:
At 4 wks, p407 and LDLR OE led to diastolic dysfunction (DD) (prolonged IVRT, decreased E/A (p<0.05 and p<0.001 respectively)), preserved EF and increased LV wall thickness (LVID and LVAW, p<0.0001). BP and WBP were normal at 4 wks but respiration (breaths per minute) decreased at 8 wks (p<0.01). ECG and AWM respectively indicated heart block and decreased exercise activity (p<0.001). With the double treatment, total cholesterol increased in heart, skeletal muscle and liver (p<0.05), while TG was decreased only in hearts (p<0.001) and liver (p<0.05). Double treatment also promoted elevated myocardial lipids, fibrosis, increased Wet/Dry lung (p<0.001) and HW/BW (p<0.05). Xanthelasma, ascites, and cardiac ischemia were noted in the double and single, p407 + luciferase groups. Sudden death (SD) occurred between 6-12 wks in double and p407+Luciferase treatment groups.

Conclusion:
We present a unique model of early onset, rapidly evolving HFpEF where double treatment mice acquire DD, arrhythmia, cardiac hypertrophy, fibrosis, pulmonary congestion, exercise intolerance, and preserved EF in the absence of obesity, HTN, CKD or DM. The model may represent a subset of HFpEF wherein hyperlipidemia drives a severe phenotype with SD as a prominent endpoint.
Abstract 12059: Speckle-Tracking Echocardiography Derived Global Circumferential Strain Predicts Adverse Outcomes in Cardiac Sarcoidosis With Preserved Ejection Fraction
Authors: Okafor Joseph , Azzu Alessia , Ahmed Raheel , Shi Rui , Ohri Shreya , Sharma Rakesh , Wechalekar Kshama , Wells Athol U , Baksi A J , Pennell Dudley J , Kouranos Vasilis , Khattar Rajdeep S
Published: June 2023

Introduction:
Risk stratification in cardiac sarcoidosis (CS) remains challenging, especially in those with preserved left ventricular ejection fraction (LVEF). Myocardial strain parameters are more sensitive than LVEF for detecting early sub-clinical myocardial dysfunction, but their prognostic value in CS is not known.

Methods:
We investigated consecutive newly diagnosed CS patients between 2015 and 2018. All patients underwent 2D echocardiography including global longitudinal strain (GLS) and global circumferential strain (GCS) measurement, cardiac magnetic resonance (CMR) for late gadolinium enhancement (LGE) and FDG-PET imaging to derive the maximum standard uptake value (SUVmax). The LGE score was quantified as the number of myocardial segments with LGE. Major adverse cardiac events (MACE) were all-cause death, sustained ventricular arrhythmia (VA), device implantation and new onset heart failure (HF) admission.

Results:
A total of 120 patients were included with age of 55±12 years; 87% were Caucasian, 43% had hypertension and 13% had diabetes. Mean LVEF was 55±12.3%, GLS was -13.4±4.2%, GCS was -16.0±5.6% and regional wall motion abnormalities (RWMA) occurred in 36% of cases. During median follow-up of 4.3 years, 43 patients experienced MACE consisting of 15 deaths, 19 VAs, 7 devices and 2 HF admissions. In multivariate analysis syncope, ethnicity, echo-derived left atrial volume and RWMA were independent predictors of MACE along with CMR-derived right ventricular EF and LGE score. Although GLS and GCS were lower in those with MACE, neither had independent prognostic value. SUVmax was also not predictive of events. In a subgroup analysis of the 86 patients with LVEF ≥50%, 20 patients experienced MACE. Multivariate analysis showed non-Caucasian ethnicity (HR 3.18 [95% CI 1.02-9.88];
P
= 0.04), RWMA (HR 3.76 [95% CI 1.29-10.98];
P
= 0.02), LGE-score (HR 1.26 95% CI 1.05-1.51];
P
= 0.01 and GCS (HR 1.18 [95% CI 1.04-1.36];
P
= 0.01) were independent predictors of MACE. A GCS value above the optimal cut-off of -16.4% was associated with a worse outcome (log-rank
P
= 0.005).

Conclusion
Ethnicity, RWMA and LGE-score are robust markers of outcome in newly diagnosed CS. Reduced GCS provides additional prognostic information in those with preserved LVEF.
Abstract 12063: Antidepressant Use and Incident Ischemic Heart Disease in Women Veterans With Posttraumatic Stress Disorder
Authors: Ebrahimi Ramin , Alvarez Carlos , dennis paul , Shroyer Laurie , Yang Hui , Perkins Aaron , beckham jean , Sumner Jennifer
Published: June 2023

Introduction:
Antidepressants, namely selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are efficacious in reducing posttraumatic stress disorder (PTSD) symptoms, but their implications for cardiovascular health are unclear. Although SSRI/SNRI treatment could improve PTSD—thus decreasing cardiovascular risk, antidepressant use has also predicted cardiovascular events. This study examined if antidepressant use was associated with developing ischemic heart disease (IHD) in women veterans with PTSD.

Methods:
The Veterans Affairs (VA) electronic health record (EHR) database was used to identify women veterans with PTSD who engaged with VA healthcare from 2000-2019. Antidepressant use (documented in the EHR) was categorized as SSRIs, SNRIs, both SSRIs/SNRIs, other, or none (ref). We used Cox regression with time-varying exposure and covariates to estimate effects of antidepressants on risk of incident IHD (angina, MI, CAD). Once a woman was exposed to antidepressants, she was considered exposed until IHD onset or censoring. Age, race, ethnicity, and a range of time-varying risk factors [traditional risk factors (e.g., hypertension), other medical risk factors (e.g., obesity), women-specific risk factors (e.g., preeclampsia), psychiatric risk factors (e.g., depression)], were covariates.

Results:
The analytic sample comprised 143,324 women without IHD at start of follow-up; mean age was 36.1 years (
SD
=11.0). Over a median follow-up of 8.6 years, there were 6,633 incident IHD cases. When adjusting for demographics and traditional IHD risk factors, exposure to SNRIs was associated with a 33% greater rate of IHD (95% CI: 1.24-1.43), SSRIs with a 27% greater rate (95% CI: 1.20-1.34), both SSRIs/SNRIs with a 59% greater rate (95% CI: 1.01-2.49), and other antidepressants with a 24% greater rate (95% CI: 1.17-1.31). Associations with SNRIs (HR=1.21, 95% CI: 1.12-1.30), SSRIs (HR=1.15, 95% CI: 1.09-1.22), and other antidepressants (HR=1.19, 95% CI: 1.13-1.26) remained significant in fully adjusted models.

Conclusions:
Antidepressant use in women veterans with PTSD may exacerbate risk of IHD. Mechanism-focused research and further work in women veterans without PTSD is also needed.
Abstract 12100: Catastrophic Large Post-Stemi Inferoseptum Ventricular Septal Rupture With Left-to-Right Shunt and an Inferoseptum Pulsatile Pseudoaneurysm
Authors: Sanchez-Nadales Alejandro , Iddrisu Muftawu-Deen , Lewis Antonio , Uppal Dipan , Neicheril Radhika , Snipelisky David , Asher Craig R
Published: June 2023

Case Presentation:
49-year-old male without known cardiovascular history presented with three days of atypical chest discomfort. 12-lead EKG revealed ST-segment elevations in II-III-aVF and depression in V1 suggestive of an acute infero-posterior MI (A), Troponin T at 6.85 ng/mL. Following administration of DAPT and heparinization, emergent coronary angiography proved a dominant RCA with proximal 60% and middle 100% occlusion (B), 80% focal stenosis at mid-LAD and 70% focal stenosis at prox-LCx (C). PCI with intra-aortic balloon pump support was performed, with two DES deployed in the RCA, use of a trans-venous pacemaker was required for complete AV block, and two defibrillations required for ventricular fibrillation. Following further hemodynamic compromise unexplained by his hemodynamic parameters, TEE was performed, demonstrating a large mid/distal infero-septum ventricular septal defect with left to right shunt (D, E and F), as well as a basal/mid infero-septum large pseudo-aneurysm (PSA) cavity (contained rupture) (G: low velocity Doppler flow from LV to PSA cavity, H and I show intact septum). The patient continued to decompensate requiring escalation to temporary mechanical circulatory support with VA-ECMO. Heart transplantation was initially considered, family decided to withdraw care due to multi-organ failure and poor prognosis

Discussion:
Due to widespread availability of primary percutaneous coronary intervention with early reperfusion, mechanical complications post MI are less common in current days. Following transmural MI, persistent hypotension and cardiogenic shock should alert for complications such as VSD or PSA. While VSD may be amenable to percutaneous or surgical closure, PSA is associated with very high mortality even if surgery is attempted. Given the presence of both a VSD and PSA, mechanical support with VA-ECMO allowed us to support the patient for several days as a bridge to decision regarding heart transplantation
Abstract 12105: Sudden Death Associated With Pregnancy
Authors: Uy-Evanado Audrey , Sargsyan Arayik S , Sorenson Chad , Chugh Harpriya , Hurst Sean , Reinier Kyndaron , Chugh Sumeet S
Published: June 2023

Introduction:
Sudden and unexpected deaths associated with pregnancy are rare but devastating occurrences in society. There is a significant lack of prospective, population-based data in the US regarding etiologies and clinical manifestation.

Hypothesis:
Prospective community-wide analyses can inform the assessment of burden as well as prevention strategies for sudden deaths associated with pregnancy.

Methods:
From the ongoing prospective, Oregon Sudden Unexpected Death Study (ORSUDS, Portland OR catchment pop. 1 M, 2002-2021) and the Prediction of Sudden Death in Multi-Ethnic Communities (PRESTO, Ventura CA catchment pop 850K, 2015-2021), we performed a detailed evaluation of all sudden death cases that occurred within 1 year of pregnancy; including lifetime clinical history, SCA presentation and resuscitation outcome.

Results:
A total of 381 (46 in PRESTO and 335 in ORSUDS) sudden deaths occurred in females aged 15 to 49 years, and 17 of these (4.5%) occurred within a year of pregnancy. Pregnancy-related cases were between 21 and 39 years of age and included 7 non-Hispanic whites, 5 Hispanic/Latinos, 1 black, 1 Native American and 3 subjects of unknown race/ethnicity. Sudden cardiac arrest occurred while pregnant (6), during delivery (2), within 3 months post-partum (5) and a miscarriage (1), and between 3 and 9 months post-delivery (3). Only witnessed cases survived (4/17, 24%) and presented with both shockable rhythm (2) and non-shockable rhythm (2). Presumptive cause of death included 10 cardiac etiologies including presumed sudden arrhythmic death (4), coronary artery disease (2), left ventricular hypertrophy (1), severe mitral valve prolapse (1), myocardial fibrosis (1) and long QT syndrome (1). Non cardiac causes included drug overdose (2), obstetric thrombo-embolism (2), cerebro-vascular accident (2), and status asthmaticus (1).

Conclusions:
Our findings suggest that pre-existing heart disease is likely to be the most important risk factor for sudden unexpected death associated with pregnancy, and warrants further detailed investigation.
Abstract 12120: Association of Physical Activity and Myocardial Fibrosis: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Zeitoun Ralph , Chehab Omar , Ma Xiaoyang , Shabani Mahsima , Varadarajan Vinithra , Wu Colin O , Florido Roberta , Post Wendy S , McClelland Robyn L , Shea Steven , Bluemke David A , Ambale-Venkatesh Bharath , Ac Lima Joao A
Published: June 2023

Introduction:
Extracellular volume (ECV), native T1 time and late gadolinium enhancement (LGE) are markers of myocardial fibrosis (MF) by cardiac magnetic resonance imaging (CMR), and are associated with CV events, HF and death. Population studies on the association of physical activity (PA) and MF have not been published.

Methods:
MESA participants with data on Moderate and Vigorous PA (MET*min/week) at Exams 1, 2, 3 or 5, and ECV (%), T1 time (ms) and presence of LGE at Exam 5 were included. We constructed participant-specific trajectories of log-transformed PA levels using nonparametric B-splines based on best linear unbiased prediction. The area under the trajectory curve was used to estimate the 10-year PA level prior to Exam 5. We explored the associations of log-transformed PA at Exam 1 (PA
1
), at Exam 5 (PA
5
) and cumulative over 10 years (PA
1-5
), with outcomes of interest (ECV, T1 time and LGE), using multivariable analysis. PA values were divided by their respective SD. Covariates included were demographic and lifestyle factors, CVD risk factors and CVD events.

Results:
A total of 2,682 participants were included (52% women, mean age 69 ± 9 years). PA
1
, PA
5
, and PA
1-5
were significantly greater in men (p<0.001 for all). PA
1
, PA
5
and PA
1-5
were not associated with ECV, T1 time or LGE in any model, for the entire cohort. Although interaction of PA
5
and PA
1-5
with sex was significant in the association with ECV, there was no significant association between PA and ECV in either men or women. Additionally, interaction of PA with sex was not significant in the association with either T1 time or LGE.

Conclusions:
In the MESA cohort, greater moderate and vigorous physical activity at baseline, at time of CMR, and cumulative over 10 years prior to CMR was not associated with ECV, native T1 time or LGE. Additionally, although interaction of PA with sex was significant in the association with ECV, there was no significant association between PA and ECV in either men or women.
Abstract 12127: Protein Disulfide Isomerase A1 as Novel Redox Sensor in VEGFR2 Signaling and Angiogenesis
Authors: Nagarkoti Sheela , Kim Young-mee N , Ash Dipankar , Das Archita , Vitriol Eric , Youn Seock-Won , Varadarajan Sudhahar , McMenamin Malgorzata , Hou Yali , Boatwright Harriet , Caldwell Ruth B , Essex David W , Cho Jaehyung , Fukai Tohru , Ushio-Fukai Masuko
Published: June 2023

Background:
VEGFR2 signaling in endothelial cells (ECs) is regulated by reactive oxygen species (ROS) derived from NADPH oxidases (NOXs) and mitochondria, which plays an important role in postnatal angiogenesis. However, it remains unclear how highly diffusible ROS signal enhances VEGFR2 signaling and reparative angiogenesis. Protein disulfide isomerase A1 (PDIA1) functions as an oxidoreductase depending on the redox environment. However, role of PDIA1 in ROS-dependent VEGFR2 signaling and angiogenesis is entirely unknown.

Results:
Here we showed that PDIA1 co-immunoprecipitated with VEGFR2 or colocalized with either VEGFR2 or early endosome marker Rab5, but not late endosome marker Rab7, at the perinuclear region in human ECs in response to VEGF. PDIA1 silencing significantly reduced VEGF-induced EC migration (43.3%), proliferation (52.8%) and spheroid sprouting via inhibiting VEGFR2 signaling. Mechanistically, VEGF stimulation rapidly increased Cys-OH formation of PDIA1 via the NOX4-mitochondrial ROS axis. Experiments using “redox-dead” mutant PDIA1 with replacement of the active four Cys residues with Ser revealed that VEGF-induced PDIA1 CysOH formation promoted angiogenic responses by increasing phosphorylation of VEGFR2 at Y1175 via oxidative inactivation of PTP1B. In vivo, Pdia1+/- mice showed impaired angiogenesis in developmental retina and Matrigel plug models as well as ex vivo aortic ring sprouting model. Hindlimb ischemia model revealed that PDIA1 expression was markedly increased in angiogenic CD31 positive ECs of ischemic muscles, and that limb perfusion recovery and neovascularization (48%) in response to ischemic injury were significantly impaired in EC-specific Pdia1 conditional knockout mice.

Conclusion:
PDIA1 can sense VEGF-induced H2O2 signal via CysOH formation to promote VEGFR2 signaling and angiogenesis in ECs via oxidative inactivation of PTP1B, thereby enhancing postnatal angiogenesis. The oxidized PDIA1 is a potential therapeutic target for treatment of ischemic vascular diseases
Abstract 12133: Coronary Artery Perforation During Chronic Total Occlusion Percutaneous Coronary Intervention: Incidence, Mechanisms, Treatment and Outcomes
Authors: Kostantinis Spyridon , Simsek Bahadir , Karacsonyi Judit , Alaswad Khaldoon , Krestyaninov Oleg , Khelimskii Dmitrii , Karmpaliotis Dimitrios , Jaffer Farouc A , Khatri Jaikirshan , Poommipanit Paul , Jaber Wissam , Rinfret Stephane , Nicholson William , PATEL MITUL P , Mahmud Ehtisham , KUTUZIS MICHAEL , Tsiafoutis Ioannis , Benton Stewart M , Davies Rhian , Toma Catalin , Kerrigan Jimmy , Haddad Elias , Abi Rafeh, MD, FACC Nidal , El Guindy Ahmed , Goktekin Omer , Mastrodemos Olga , Rangan Bavana V , Burke M Nicholas , Brilakis Emmanouil S
Published: June 2023

Introduction:
Coronary artery perforation is a feared complication of chronic total occlusion (CTO) percutaneous coronary intervention (PCI).

Methods:
We analyzed the baseline clinical and angiographic characteristics and procedural outcomes of 10,454 CTO PCIs performed in 10,219 patients between 2012 and 2022.

Results:
The incidence of coronary perforation was 4.9% (n=503). Patients who experienced coronary perforation were older and were more likely to have had prior coronary artery bypass graft surgery. Procedures that resulted in perforation were more complex, with higher J-CTO and PROGRESS-CTO scores. Technical (66% vs. 87%; p<0.01) and procedural (55% vs. 87%; p<0.01) success rates were lower among perforation cases. The most common site of perforation was the CTO target vessel (66%), the retrograde approach was responsible for the perforation in 47% of the cases and guidewire exit was the most common mechanism of perforation. The proportion of Ellis Class 1, 2, 3 and 3 -“cavity spilling” coronary perforations was 20%, 41%, 28% and 11%, respectively. In 52% of perforations, one or more interventions were required: prolonged balloon inflation (23%), covered stent deployment (21%), coil embolization (6%) and/or autologous fat embolization (4%). Tamponade requiring pericardiocentesis occurred in 69 patients (14%). The incidence of major adverse cardiovascular events (MACE) was higher in perforation cases (18.1% vs. 1.3%; p<0.01).

Conclusions:
Coronary artery perforation occurred in 4.9% of CTO PCIs performed by experienced operators and was associated with lower technical success and higher in-hospital MACE.
Abstract 12138: Outcomes of Pediatric Cardiac Transplantation With a Positive Retrospective Crossmatch
Authors: Lytrivi Irene D , Cantor Ryan , esteso paul , Frandsen Erik L , Gibbons Meredith K , Kirklin James K , Koehl Devin , Lamour Jacqueline M , Putchoegl Adam , Shugh Svetlana B , Williams Ryan J , Pearce Frank B
Published: June 2023

Introduction:
A positive crossmatch (+ XM) has traditionally been associated with adverse outcomes following pediatric heart transplantation. However, more recent studies suggest that favorable intermediate-term outcomes may be achieved despite a + XM.

Hypothesis:
Children with a + XM have similar long-term survival but higher rate of complications, such as rejection, coronary vasculopathy (CAV), and infection, compared to patients with a negative XM.

Methods:
The Pediatric Heart Transplant Society Registry database was queried from 2010-2021 for all patients <18 years of age with a known XM. Baseline demographics were compared between + XM and negative XM groups using appropriate parametric and non-parametric group comparisons. Multiphase survival analysis curves were constructed for each outcome to describe both short- and long-term hazard. Similar correlations were performed for different types of + XM (cytotoxic vs Flow).

Results:
Of 4599 transplants during the study period, XM results were available for 3914, with + XM in 373 (9.5%). There were 70 cases with CDC + XM (39 B-cell, 31 T-cell) and an additional 149 (90 B-cell, 59 T-cell) with flow + XM where CDC XM was either negative, unknown, or not performed. 5-year survival was significantly different in the 2 groups (HR=1.3, p=0.04). Patients with a +XM had shorter time to first rejection (p=.0001) and detection of CAV (p=0.01), while the risk of infection was similar (p=0.11) [Figure]. When comparing CDC+ to Flow+/CDC- patients, there was no difference in 5-year survival or time to first rejection, however CDC+ patients had shorter time to CAV detection (p= 0.01).

Conclusions:
Pediatric patients transplanted across a + XM experience earlier rejection, earlier development of CAV, and increased graft loss compared to patients with a negative crossmatch. The risk of heart transplantation against a + XM must be balanced with the ongoing risk of waitlist mortality.
Abstract 12165: Transcatheter Mitral Valve Repair is Safe in Older Adults: Insight From the Nationwide Inpatient Sample Database
Authors: Fadah Kahtan , Winchester David E
Published: June 2023

Introduction:
Transcatheter mitral valve repair (TMVR) is an effective treatment for symptomatic mitral insufficiency, however in elderly patients is limited. We compared outcomes clinical outcomes, cost, and complications in adults aged ≥80 years old compared to < 80 years old.

Methods:
We identified all cases of transcatheter mitral valve repair in patients admitted to hospitals in the United States (US) from 2016 to 2019 using the National Inpatient Sample. We compared outcomes between older adults and younger population using 79 years of age as the cutoff.

Results:
Out of 3130 patients who underwent TMVR , 33.42 % of patients were over the age ≥80 of years. Half of those patients were female (49.91%). Older patients ≥80 years of age were more likely to have congestive heart failure (79.36 versus 70.13, p<.0001), dyslipidemia (57.64% versus 51.0%, p<.0001), chronic kidney disease (34.66% versus 25.39%, p<.0001), and coronary artery disease (58.51% versus 51.141%, p<.0001). While patients younger than 80 years of age more frequently had diabetes mellitus(29.83% versus 19.92%, p<.0001), hypertension (30.12% versus 21.30%, p<.0001), and smoking(9.09% versus 0.72%, p<.0001). Hospital mortality was lower in patients 80 years of age or older (2.56% versus 4.46%, p<.0001). In addition, hospital length of stay and total charges were lower in the older group (4.93±6.62 days versus 10.85±13.61 days), and ( $222933 ±155969 versus $288776 ±314288, p <.0001). However, multivariable analysis after adjusting for baseline comorbidities mentioned above did not show significant difference in mortality between the two groups (OR 0.792, CI 0.501-1.252).

Conclusions:
After adjustment for baseline characteristics, patients ≥80 years old and undergoing TMVR have similar in-hospital mortality to patients under age 80. Care for the ≥80 cohort was more costly. The present analysis suggests TMVR is safe in older adults.
Abstract 12182: Cardiac Transcriptome Remodeling and Impaired Bioenergetics in Single Ventricle Congenital Heart Disease
Authors: Garcia Anastacia M , Toni Lee S , Sparagna Genevieve C , Jonscher Raleigh , Karimpour-Fard Anis , Baybayon-Grandgeorge Angela N , Pietra Ashley E , Stauffer Brian L , Sucharov Carmen C , Miyamoto Shelley D
Published: June 2023

Introduction:
Single Ventricle congenital heart disease (SV) encompasses a group of cardiac abnormalities where improper development of the heart results in only one functional pumping chamber. From a molecular standpoint, how the myocardium adapts to the chronic altered hemodynamic conditions of SV physiology, and the mechanisms implicated in the transition to heart failure (HF) which is common in the SV population, are poorly understood. Here, we test the hypothesis that metabolic remodeling represents a pathophysiologic mechanism of heart failure progression in SV.

Methods:
We performed comprehensive multi-omics analysis (transcriptomics, metabolomics, and lipidomics) of the SV myocardium from both failing (SVHF, N=15) and non-failing (SVNF, N=9) SV subjects, compared with biventricular non-failing controls (BVNF, N=4). Furthermore, we assessed functional components of mitochondrial bioenergetics in each of these populations.

Results:
Integrated multi-omics analysis demonstrated dysregulation of multiple metabolic pathways in the failing SV heart (A). Functional cardiac bioenergetics analysis revealed decreased mitochondrial carnitine palmitoyl transferase activity (B) and mitochondrial dysfunction (C), with corresponding decreases in tricarboxylic acid cycle metabolites, high energy phosphates, and lipid intermediates in the failing SV heart. Moreover, some of these bioenergetic perturbations precede the onset of overt failure, and are seen in the non-failing SV heart (B-C).

Conclusions:
Our findings indicate that SV physiology induces myocardial metabolic alterations that limit mitochondrial fatty acid β-oxidation and decrease cardiac energy generation. Together, these data suggest SV patients may be uniquely vulnerable to changes in energetic demand and may benefit from therapeutic strategies aimed at preserving cardiac bioenergetics and preventing cardiometabolic remodeling for the treatment or prevention of HF.
Abstract 12185: Medication Changes And Reasons For No Medication Change Among Outpatients With Heart Failure With Reduced Ejection Fraction: Results From CHART-HF
Authors: Greene Stephen J , Gaggin Hanna K , Lautsch Dominik , Song Yan , Signorovitch James , Stevenson Andra S , Blaustein Robert , Zhou Mo , Butler Javed
Published: June 2023

Introduction:
Underuse and under-dosing of guideline-directed medical therapy (GDMT) for HFrEF in US outpatient practice is well documented. Yet changes to GDMT and clinician-reported reasons for not making medication changes are not well described.

Methods:
US cardiologists were recruited from the Schlesinger Group, a nationwide panel of physicians who participate in web-based surveys. The cardiologists conducted anonymized chart reviews of their own randomly selected patients meeting eligibility criteria. Eligible patients had HFrEF<45% without end-stage kidney disease, and an outpatient cardiology visit between 2017-2019. For each index outpatient visit, cardiologists abstracted data on medication changes and reported their primary rationale for not making a change in each specific therapy.

Results:
Overall, 238 cardiologists participated and reviewed outpatient visits for 458 patients under their care (median age 64 years, 65% male). Before the index visit, proportions of patients not prescribed beta-blocker, MRA, ARNI, and SGLT2i were 17%, 58%, 72%, and 86%, respectively. Across medications, proportions of patients with medication initiation ranged from 5-11%, medication discontinuation from 0-11%, with variable rates of dose changes
(Figure, Panel A).
Among patients receiving medication, for each therapy, the most common clinician-reported reason for no medication change was patient clinical stability (43-57%). Other reasons for no medication change included already being at target dose (29-44% of cases), and perceived risk of intolerance (6-11%)
(Figure, Panel B)
.

Conclusions:
We observed relatively few medication changes made among these HFrEF patients. Patient stability and perceived risk of intolerance were frequently cited by cardiologists as reasons for not making guideline-directed medication changes, suggesting clinical inertia as a major barrier to closing gaps in GDMT.
Abstract 12208: Acute Nitroglycerin Use Worsens Ventilatory Efficiency in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Balmain Bryce N , Tomlinson Andrew R , MacNamara James P , Sarma Satyam , Wakeham Denis J , Morris Margot , Moran Raksa B , Payne Marcus , Samels Mitchel , Levine Benjamin D , Babb Tony G
Published: June 2023

Introduction:
The marked rise in left ventricular (LV) filling pressure (ie., pulmonary capillary wedge pressure [PCWP]) during exercise and its association with adverse prognosis in patients with heart failure with preserved ejection fraction (HFpEF) has stimulated interest in therapies to decrease LV filling pressures. Although reducing LV filling pressure may improve exercise hemodynamics, this may also reduce pulmonary perfusion (Qc) and increase ventilation-perfusion (V/Q) mismatch, manifesting as an increase in ventilatory inefficiency during exercise (ie., slope of the ventilation [V̇
E
] and carbon dioxide elimination [V̇CO
2
] relationship), which is a strong prognostic indicator of adverse outcomes in heart failure.

Hypothesis:
Reducing PCWP via acute nitroglycerin (NTG) treatment would increase the V̇
E
/V̇CO
2
slope when compared with a placebo treatment in patients with HFpEF.

Methods:
26 subjects were evaluated (age: 69±5y; BMI: 39.5±7.1kg/m
2
; V̇O
2peak
: 1.39±0.46L/min; 16 women/10 men). All subjects performed a six-minute constant-load cycling test at 20W with placebo or NTG treatment. PCWP was measured via a right-heart catheter, arterial blood gases were measured via a radial artery catheter, Qc was measured via direct Fick, and pulmonary gas exchange was measured via a customized breath-by-breath metabolic system. The V̇
E
/V̇CO
2
slope was calculated as the relation between the rest-to-20W change in V̇
E
and the rest-to-20W change in V̇CO
2
.

Results:
PCWP decreased with NTG at 20W (placebo: 20.8±5.8 vs. NTG: 16.4±5.1 mmHg, p=0.001). Qc also decreased with NTG at 20W (placebo: 8.69±1.84 vs. NTG: 8.26±1.87 L/min, p=0.01). In contrast, the V̇
E
/V̇CO
2
slope increased with NTG (placebo: 37.5±5.8 vs. NTG: 39.6±7.0, p=0.01).

Conclusions:
These findings suggest that reducing LV filling pressure increases ventilatory inefficiency, possibly due to an increase in V/Q mismatch caused by a reduction in pulmonary perfusion. Since therapies to decrease LV filling pressure have gained considerable interest to improve exercise hemodynamics in HFpEF, further investigation is required to determine the clinical consequences of ventilation-perfusion mismatch and ventilatory inefficiency caused by a reduction in PCWP in these patients.
Abstract 12216: Prevalence of Coronary Microvascular Dysfunction in Patients With Angina and Known Myocardial Bridge
Authors: Allan Tess , Henry Michael , Patel Amit , Balkhy Husam H , Blair John
Published: June 2023

Introduction:
Myocardial bridges are prevalent in patients with and without angina and can present a diagnostic dilemma when evaluating angina. Coronary microvascular dysfunction (CMD) is an important cause of chest pain in patients presenting with angina without obstructive CAD. The prevalence of concomitant CMD and myocardial bridge is not well described.

Methods:
All patients with known myocardial bridge and chest pain who underwent cardiac catheterization with bridge study at the University of Chicago Medical Center between 2020-2021 were included. All patients underwent pharmacologic testing with dobutamine with measurement of resting flow reserve (RFR). Abnormal RFR was defined as < 0.8. Some patients additionally underwent coronary physiology study with adenosine (Ado) and/or acetylcholine (Ach) with determination of coronary flow reserve (CFR), index of microvascular resistance (IMR), and spasm (for Ach). Abnormal endothelial dependent microvascular function was defined as CFR < 1.5 or IMR > 31 on Ach testing. Abnormal endothelial independent microvascular function was defined as CFR < 2.0 or IMR > 25 on Ado testing.

Results:
A total of 27 patients (mean age 47
+
9, 60% female) were studied. There were 18 patients with hemodynamically significant bridge of whom 13 underwent surgical unroofing and 9 patients with hemodynamically insignificant bridge of whom 3 underwent surgical unroofing. There was no significant difference in rates of endothelial dependent or independent CMD or angiographic spasm between groups. Further coronary endotype data is displayed in Table 1.

Conclusion:
Endothelial dependent and independent microvascular dysfunction are prevalent in patients presenting with known myocardial bridge and chest pain and rates are not affected by hemodynamic significance of the bridge. Knowledge of coronary endotype in patients with myocardial bridge may assist in tailoring therapies to improve chest pain.
Abstract 12278: Relationship Between Amiodarone Response Prior to Ablation and One Year Outcomes of Catheter Ablation for Atrial Fibrillation
Authors: Yadav Ritu
Published: June 2023

Introduction:
Catheter ablation for atrial fibrillation is a common therapeutic strategy for paroxysmal and persistent AF patients, but long-term success rates are imperfect. Maintenance of sinus rhythm prior to ablation with antiarrhythmic drug therapy has improved outcomes in patients undergoing ablation compared to ablation procedure alone. Amiodarone has superior efficacy relative to other AADs. Whether the failure of amiodarone to maintain sinus rhythm prior to ablation is a predictor of poor outcomes is unknown.

Methods:
Total 307 patients received amiodarone in a span of 1y before undergoing catheter ablation for AF from January 2014 to March 2019. Patients were divided into amiodarone success (n=183) and amiodarone failure (n=124) groups based on the response to pre-ablation amiodarone treatment. Follow-up was done for 12 months post-ablation to assess outcomes (arrhythmia recurrence and adverse events). Procedural success was defined by the absence of documented arrhythmia (>30s) without any antiarrhythmic agents beyond a 90d blanking period.

Results:
Ablation procedure success rate at 1y was 57.7% overall. 1y success rate in the amiodarone success group was comparable to that in the amiodarone failure group (55.7% vs. 60.5%; p=0.54). Success rates following ablation did not vary by the response to amiodarone when analyzed for paroxysmal or persistent AF subgroups.

Conclusion:
Failure to restore and maintain sinus rhythm on amiodarone therapy is not a predictor of adverse ablation procedure outcomes and should not be used as a patient selection criteria for consideration of ablation.
Abstract 12286: A Novel Yap Inhibitor Cbl0137 Protects Against Endothelial Inflammation and Atherosclerosis
Authors: Ding Huanyu , Jiang Minchun , Wang Li , Huang Yu
Published: June 2023

Background:
Endothelial activation is a critical hallmark in the initiation of atherosclerosis. Our previous study found that YAP activation plays a significant role in induction of endothelial inflammation and formation of atherosclerotic plaques, suggesting that targeting YAP signaling pathway might be effective for the treatment of atherosclerotic cardiovascular disease. We have recently set up a reporter gene assay-based drug screening platform and identified CBL0137 as an inhibitor of YAP activity in human endothelial cells.

Methods:
We used 8*GTIIC luciferase reporter gene assay to screen a drug library and other small molecule compounds. We validated the inhibitory effect of CBL0137 on YAP activity by detecting the expression of YAP target genes and phosphorylation of YAP, which were measured by quantitative real-time polymerase chain reaction and western blotting, respectively. Subsequently, we treated human endothelial cells with CBL0137 (1 μM) for 4 hrs, and then isolated the total RNA and performed transcriptome sequencing. We explored the anti-inflammatory effects and underlying mechanisms of CBL0137 in primary endothelial cells. Moreover, we assessed whether CBL0137 could retard formation of atherosclerotic plaques in ApoE-/- mice using carotid artery partial ligation-induced and chronic western diet-induced atherosclerosis models.

Results:
We identified CBL0137 as a novel YAP inhibitor through screening the drug library. In human endothelial cells, CBL0137 inhibited the phosphorylation of YAP at Y357 to suppress YAP activity, and therefore repressed the expression of YAP target genes. In addition, CBL0137 restrained endothelial inflammatory response in a YAP-dependent manner. Furthermore, CBL0137 inhibited YAP phosphorylation at Y357 via the tyrosine-protein kinase Src. In animal experiments, administration of low doses of CBL0137 attenuated endothelial inflammation and atherosclerosis induced by disturbed flow or atherogenic diets in both male and female ApoE-/- mice.

Conclusions:
CBL0137 is a novel YAP inhibitor that protects against endothelial inflammation and atherogenesis. CBL0137 might be a promising anti-atherosclerosis drug, but further investigations including clinical trials are required.
Abstract 12297: Kissing Left Atrial Appendage Closure Devices for Peri-Device Leak
Authors: Lee Bridget , Brider Jamarcus , Doty Brandon , Al-Hindi Feross , Nair Devi
Published: June 2023

Introduction:
Left atrial appendage closure (LAAC) therapy is approved for stroke prevention in nonvalvular atrial fibrillation (AF) for patients intolerant in long term oral anticoagulation (OAC). Peri-device leak (PDL) is the achilles heel to optimal LAAC and increases stroke risk. Here, we describe the novel use of a second LAAC device for closure of a large PDL in a bilobar appendage.

Case:
A 66-year-old male with a history of nonvalvular AF with recurrent bleeding on OAC with Watchman 2.5 implant six years prior, presented to our facility for a repeat AF ablation. Pre-procedural imaging showed a PDL of 12 mm with an uncovered posterior lobe, with the Watchman 2.5 covering only the anterior lobe of the appendage. The PDL was closed with a 20 mm Amulet device delivered through a steerable sheath abutting the existing Watchman 2.5 device. The steerability of the sheath allowed for optimal placement of the Amulet device to allow for complete closure. Patient was discharged home on six weeks of dual antiplatelet therapy.

Discussion:
In our case, a second LAAC device was chosen due to the large size of the PDL. Smaller leaks can be closed using endovascular coils and/or occluder plugs. Larger leaks require additional consideration for closure strategies such as a second LAAC device

Conclusions:
Our case is the first reported case utilizing a second LAAC device for PDL closure alongside the first device. Steerability of the new Amulet sheath allowed for optimal device placement for complete closure. Additional research is needed on how PDL’s should be addressed for optimal LAAC.

Figure 1: Imaging showing PDL into uncovered posterior lobe

Figure 2: Complete LAAC with kissing Watchman 2.5 and Amulet
Abstract 12300: Circulating Gut-Microbiota-Related Metabolite Phenylacetylglutamine Levels, Diet Quality, and Risk of Incident Coronary Heart Disease Among Women
Authors: Heianza Yoriko , Wang Xuan , Tiwari Saumya , Watrous Jeramie , Rexrode Kathryn M , Sun Qi , Jain Mohit , Manson Joann E , Qi Lu
Published: June 2023

Introduction:
Phenylacetylglutamine (PAGln) has been recently discovered as a gut-microbiota-related metabolite, and circulating PAGln may be related to risks of cardiometabolic abnormalities. Gut microbiota-related dietary intakes and high-protein foods may affect circulating PAGln levels.

Hypothesis:
We assessed whether circulating PAGln levels may be related to intakes of gut-microbiota-related food intakes, and higher levels of PAGln may be associated with greater degrees of cardiometabolic abnormalities. We also tested a hypothesis that higher levels of circulating PAGln may be related to higher risk of the incident coronary heart disease (CHD).

Methods:
Circulating levels of PAGln, diet assessed using 7-day dietary records, and cardiometabolic abnormalities were assessed in the Women's Lifestyle Validation Study (WLVS) (n=723). The associations between plasma PAGln levels and risk of incident CHD were analyzed in a prospective nested case-control of 1520 women (760 incident cases of fatal CHD and nonfatal myocardial infarction and 760 controls) from the Nurses’ Health Study (NHS). We identified incident cases of CHD over 10-14 years of follow-up time.

Results:
Higher levels of PAGln were associated with higher levels of circulating insulin, triglycerides, as well as lower levels of HDL cholesterol. We found that greater intakes of red meat and processed meat (p=0.01), but not of poultry or fish (p >0.05), and lower intakes of vegetables (p=0.03) were significant factors associated with higher levels of circulating PAGln. In the prospective nested case-control study setting, higher levels of PAGln were associated with higher risk of the incident CHD. Every 1 unit increment of log-transformed PAGln was associated with a relative risk of 1.21 (95% CI: 1.01, 1.45) for the incident CHD.

Conclusions:
Gut-microbiota-affecting diet quality were related to circulating levels of PAGln. Circulating PAGln levels may be associated with cardiometabolic abnormalities and risk of incident CHD among women.
Abstract 12305: Cardiac Computed Tomography Derived Aorta and Aortic Arch Z-scores in Children
Authors: Donthula Rakesh , Kaur Harmanpreet , Li Wen , uppu santosh
Published: June 2023

Introduction:
Echocardiogram, Cardiac Magnetic Resonance Imaging, and Computed Tomography Angiography (CTA) play a key role in the diagnosis and follow-up of congenital heart disease patients. Our objective was to establish CTA-derived normative data for aortic root (AoR), aortic sinotubular junction (STJ), ascending aorta (AAO), proximal (PAA), distal transverse aortic arch (DAA), isthmus (Is), and descending aorta (DAO) in children.

Methods:
Maximum, minimum, and mean diameters for STJ, AAO, PAA, DAA, Is, and DAO in systole and diastole were measured in 100 subjects who had CTA between January 2015 through December 2020 with no intracardiac defect or shunt lesion. The allometric exponent (AE) for each parameter was derived, and the parameter/body surface area (BSA)^AE is established using previously described methods. Regression analysis is performed to demonstrate a linear relationship to BSA. Using this data, normalized mean and standard deviation (SD) are calculated for all the structures mentioned and z-score curves are plotted in relation to BSA.

Results:
The normalized mean diameters (mm) in systole for AoR is 19.67 ± 1.99, STJ 17.25 ± 1.77, AAO 17.73 ± 2.18, PAA 16.39 ± 2.05, DAA 15.32 ± 1.75, Is 14.25 ± 1.69, and DAO 12.46 ± 1.64. For diastole, AoR is 18.87 ± 1.83, STJ 16.39 ± 1.77, AAO 16.39 ± 2.07, PAA 15.04 ± 2.13, DAA 14.22 ± 1.78, Is 13.26 ± 1.58, and DAO 11.66 ± 1.33. The figure shows the z-score plots.

Conclusions:
This is the first study in children that provides normative CTA-derived data for the AoR, STJ, AAO, PAA, DAA, Is, and DAO. This data is helpful to guide medical and surgical decision-making in children with congenital heart disease.