bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 14949: Wear Time, Frequency of and Time to First Atrial Fibrillation Detection in Patients With a History of Stroke
Authors: Parikh Purvee , Gillstrom Grant , Norlock Vincent , Grigoriadis CJ , Dunn Alexandria , Wadhwa Manish
Published: June 2023

Introduction:
Telemetry monitoring following cryptogenic stroke (CS) is routinely undertaken to rule out atrial fibrillation (AF) as a stroke source. In patients with stroke of known etiology, AF may represent an alternate mechanism for the incident stroke and predicate anticoagulation. Irrespective of classification, a potential limitation of post-stroke monitoring is the patients’ ability to wear an ambulatory monitor for an extended timeframe.

Aim:
Identify mobile cardiac outpatient telemetry (MCOT, Philips BioTel Heart) monitor wear time, frequency of AF detection, and time to first AF diagnosis in patients with any history of stroke.

Methods:
A retrospective review of 7,426 patients prescribed 30-day MCOT with ICD-10 diagnosis codes starting with I63 (cerebral infarct, unspecified) was conducted. Data from 2021 was analyzed for MCOT monitor wear time, occurrence of any AF, and time to first AF detection. Monitor wear time was defined as the time from the first to the last telemetry transmission.

Results:
The percentage of patients with MCOT monitor wear time of 5, 10, 15, 20, 25 and 30 days was 93%, 87%, 82%, 76%, 67% and 44%, respectively. In this cohort, 748 patients (10.1%) were identified with any AF. Of these patients, the first AF detection occurred in 33% (3.3% of total) in days 1-5 of monitoring, 20% (2.0%) in days 6-10, 15% (1.5%) during days 11-15, 14% (1.4%) during days 16-20, 9% (0.9%) during days 21-25, and 9% (0.9%) during days 26-30. Interestingly, 4% of AF detection (0.4% total) occurred on days 29-30.

Conclusions:
Patients with cerebral infarcts are capable of adhering to extended MCOT wear times, and 10% of patients with any history of stroke demonstrated AF when prescribed MCOT for 30 days. While most patients had first AF detection within 15 days, 32% of patients had first AF detection between days 16-30. These findings suggest that patients with any history of stroke, regardless of etiology, may benefit from extended duration telemetry monitoring.
Abstract 14997: Computerized Cognitive Training and 24-Month Mortality in Heart Failure
Authors: Jung Miyeon , Giordani Bruno , Smith Asa B , Clark David G , Gradus-Pizlo Irmina , Wierenga Kelly L , Pressler Susan J
Published: June 2023

Introduction:
Long-term efficacy has not been widely evaluated for computerized cognitive training (CCT) to improve cognition and reduce mortality. The purpose of this study was to evaluate long-term efficacy of CCT to reduce risk of death and test additional predictors of long-term mortality among patients with heart failure (HF).

Methods:
In this prospective study, a subset of 142 patients with HF were included from the parent 3-arm RCT testing CCT using BrainHQ to improve memory. Mortality data were collected from electronic health records, family caregivers, physicians or nurses during 24 months after the randomization between Mar 2017 and Dec 2020. Multiple logistic regressions were performed with 2 predictor variables (group and an additional predictor) given the small number of death cases. Predictors tested were age, baseline global cognition, memory, working memory, depressive symptoms, and health-related quality of life (HRQL).

Results:
The sample was 52% women/48% men; mean age 65 (SD=13) years; and race 13% Black, 1% more than one race, 1% Native Hawaiian/Pacific Islander, and 85% White. Mean left ventricular ejection fraction was 46% (SD=14). Of 142 patients, 16 (11.3%) died; 4 (8.3% of 48) in CCT group and 12 (12.8% of 94) in control groups (p=.429). The patients who died were older by 9 years (p=.002), had more depressive symptoms (p=.022), and poorer global cognition (p=.009), memory (p=.069), and HRQL (p=.080) at baseline. In logistic regression models, CCT group was not a statistically significant predictor of 24-month mortality (OR=0.65, 95% CI=0.28-1.15). Patients with better global cognition and memory were less likely to die over 24 months by 27% (OR=0.73, 95% CI=0.58-0.90) and 19% (OR=0.81, 95% CI=0.67-0.99), respectively. Patients with more depressive symptoms (OR=1.10, 95% CI=1.00-1.21) and older age (OR=1.08, 95% CI=1.01-1.14) were more likely to die over 24 months. Working memory and HRQL did not predict mortality.

Conclusions:
CCT using BrainHQ did not show long-term efficacy on reducing 24-month mortality in HF. Efficacious interventions are needed that are targeted at underlying etiologies of cognitive dysfunction and depressive symptoms in older patients with HF.
Abstract 15011: Deriving and Validating Novel Neighborhood Data for Investigation of Adverse Outcomes in Patients Hospitalized for Heart Failure: A Feasibility Study
Authors: Zhang Juhao , Lin Samantha , Wu Yunjie , Zhang Jing , Morris Alanna A , Patel Shivani A , Ho Joyce C
Published: June 2023

Introduction:
Census-based measures of population-level neighborhood deprivation have been linked to adverse outcomes in patients with heart failure (HF). However, limited data exist to examine the impact of neighborhood environmental characteristics on HF outcomes.

Objective:
Derive novel measures of the patient built environment using multiple databases and compare their performance with traditional Census-based measure of population deprivation to predict 30-day readmission following hospitalization with HF.

Methods:
We identified the 17 census tracts in the metropolitan Atlanta area from the lowest, middle, and highest tertiles of the Social Deprivation Index (SDI), a neighborhood deprivation measure derived from US Census data. Three novel data sources—Twitter, Foursquare, and Google Places—were used to compute 6 environmental scores in each census tract: accessibility to parks, pharmacies, grocery stores, restaurants, sports places (e.g., gyms and fields), and health facilities (e.g., clinics and hospitals). We computed Pearson correlations across the data sources. We examined model performance of the 6 environmental scores and the SDI to predict readmissions in 804 patients (mean age 67 y, 52% female, 77% Black) hospitalized for acute HF at Emory Healthcare in 2018 using logistic regression adjusted for patient demographic and clinical characteristics.

Results:
Correlations across data sources ranged from
r
=-.45 to .65 (Figure 1a). Compared with SDI, 4 of the 6 environmental measures yielded marginally higher AUC values (discrimination) and 2 yielded higher pseudo R-squared values (calibration) for 30-day readmission (Figure 1b).

Conclusion:
This study demonstrates the early feasibility of directly measuring the patient built environment using novel data streams, and shows that these data may enhance neighborhood understanding of HF outcomes. Future studies should focus on scaling beyond the metropolitan Atlanta area.
Abstract 15015: Long Term Outcomes After Interrupted Aortic Arch Repair: A Study From the Pediatric Cardiac Care Consortium
Authors: Miller Jamison C , Velani Romie , Miller Wade D , Thomas Amanda S , Kochilas Lazaros
Published: June 2023

Introduction:
Interrupted aortic arch (IAA) is a congenital heart disease that can be successfully repaired. Children are at risk of multiple procedures and residual abnormalities. We used the Pediatric Cardiac Care Consortium (PCCC) to describe post-repair survival of patients with IAA.

Methods:
We queried the PCCC for patients receiving IAA repair 1982-2003. Death was ascertained from the PCCC and US National Death Index (NDI) to December 2019. Kaplan Meier (KM) plots and multivariable analysis assessed overall long-term survival and baseline characteristics associated with increased hazard of death post-repair.

Results:
We identified 380 patients (male 200; female 180) with IAA repair (excluding truncus arteriosus). Most had end-to-end anastomosis (n=234, 83.6%), 87 (31.1%) by interposition graft, and 47 (16.78%) by subclavian or carotid flap. There was no data for 11 patients. A total of 280 survived to discharge. Over a median of 22.9 years (IQR 19.78-27.52 years), 39 died. The 25-year survival post-discharge after repair was 86% (Figure 1). Type B2 IAA (aberrant right subclavian artery) was associated with increased death (aHR=1.814; 95% CI=0.891-3.694) versus non-type B IAA and cases with normal subclavians (A1+B1)) after adjusting for era, sex, presence of chromosomal anomalies, and type of surgery. Interposition graft was associated with increased hazard versus end-to end anastomosis (aHR=1.942; 95% CI=0.946-3.988) or vascular flaps (aHR=1.144; 95% CI=0.456-2.870). Other risk factors were female sex and chromosomal anomalies (DiGeorge syndrome primarily) (aHR = 1.948; 95% CI=0.946-4.011 and aHR=1.090; 95% CI=0.429-2.770).

Conclusions:
Patients with repaired IAA have decreased long-term survival. Female sex, chromosomal anomalies, type B IAA, aberrant right subclavian artery, and interposition graft were risk factors for poor long-term outcomes. Additional analysis of risk factors for long-term outcomes and causes of death is underway.
Abstract 15024: High Concentration Mineral Oil, Corn Oil and Their Constitutive Fatty Acids Do Not Influence Low-Density Lipoprotein (LDL) Oxidation Rates
in vitro
Authors: Sherratt Samuel C , Libby Peter , Bhatt Deepak L , Mason Preston
Published: June 2023

Introduction:
LDL transports dietary long chain fatty acids, constituents that may influence rates of lipid oxidation. Modified LDL promotes foam cell formation during atherosclerosis. The omega-3 fatty acid (n3-FA) eicosapentaenoic acid (EPA) administered as icosapent ethyl (IPE), reduced cardiovascular events in REDUCE-IT compared to mixed n3-FAs in similar high-risk patients (STRENGTH). Some have attributed these discordant outcomes, in part, to placebo choice (mineral versus corn oil) despite very limited oral absorption. We compared the effects of these oils and various FAs on rates of LDL oxidation at supra-pharmacologic doses.

Methods:
LDL was isolated from human plasma by isopycnic centrifugation, separated into test samples of 100 μg/mL before being incubated at 37°C for 30 min with pharmaceutical grade mineral or corn oil at high concentrations (100 μg/mL) that are comparable to treatment achieved n3-FAs (4 g/d) that have high oral absorption. We also tested FAs contained in these oils, including stearic acid (18:0), arachidic acid (20:0), and linoleic acid (18:2, n-6) as well as ascorbic acid (10 μM) and a water-soluble analog of vitamin E (Trolox, 10 μM) as controls. All samples then underwent copper-induced oxidation (20 μM) monitored by formation of malondialdehyde (MDA).

Results:
MDA formation increased from 0.28 ± 0.03 to 9.96 ± 0.58 μM (
p
<0.001) with vehicle treatment from 0-2 h. Addition of either mineral or corn oil at 100 μg/mL did not significantly influence rates of MDA formation at 2 h (0.02% and 1.93% change vs vehicle, respectively). Nor did we observe any antioxidant activity with constituent FAs stearic acid, arachidic acid, or linoleic acid, FAs with no or two double bonds. As antioxidant controls, ascorbic acid and Trolox both reduced LDL oxidation by 93% and 94% (0.71 ± 0.11 and 0.62 ± 0.04 to 9.96 ± 0.58 μM,
p
<0.001) after 2 h.

Conclusions:
Neither mineral nor corn oils affected LDL oxidation even at supra-pharmacologic concentrations. Beyond poor oral absorption, mineral oil and its constituent fatty acids did not affect LDL oxidation, a property related to mechanisms of atherosclerosis.
Abstract 15027: Senescence-Associated Pathway Activation in Cardiac Fibroblasts in Dilated Cardiomyopathy
Authors: Antolic Andrew , Shin Yoon J , Kleinhenz Jennifer M , Jiao Zhe , Hecker Louise A , Burke Michael A
Published: June 2023

Introduction:
Cardiac fibrosis is a pathologic driver in heart failure (HF) and aging is a major risk factor for HF. Persistence of activated myofibroblasts is a key feature of pathological fibrosis. In an aging model of lung fibrosis, senescent myofibroblasts exhibit apoptosis-resistance, which contributes to the sustained fibrotic response. Therapeutic targeting of NADPH oxidase-4 (NOX4), a primary source of reactive oxygen species (ROS) in myofibroblasts, can inhibit fibrosis development and reverse established lung fibrosis. We sought to understand the role of cellular senescence and NOX4 activation and persistence of cardiac fibroblasts with progression to HF.

Methods and Results:
Mice carrying a mutation in the phospholamban gene (PLNR9C) develop progressive dilated cardiomyopathy (DCM), extensive cardiac fibrosis and HF. Using the Langendorff hanging heart method and flow cytometry, cardiac fibroblasts were isolated and studied for markers of cellular senescence. Cardiac fibroblasts from PLNR9C mice with DCM display a senescent phenotype, with significantly elevated levels of the senescence markers p16 (2.1-fold, p<0.01, n=3, Figure) and beta-galactosidase (1.7-fold, p<0.01, n=3), along with significantly increased ROS production (Amplex Red assay 2.5-fold, p<0.01, n=3), as compared to fibroblasts from age-matched wild type (WT) mice. Nox4 is upregulated in cardiac fibroblasts from PLNR9C mice (mRNA 8.5-fold, n=4, p<0.01; protein 5.0-fold, p<0.01, n=4, Figure) with HF but not in young PLNR9C mice prior to development of DCM.

Conclusions:
These data reveal a premature aging phenotype in cardiac fibroblasts from mice with genetic DCM and identify NOX4 as a putative mediator of fibroblast activation and persistence.
Abstract 15039: International Multicenter Registry Study of Patients With Variants in
ATP1A3
-Encoded Sodium-Potassium ATPase 3 Finds an Association With Short QT and Life-Threatening Ventricular Arrhythmias
Authors: Moya-Mendez Mary E , Bidzimou Minu-Tshyeto , Ezekian Jordan E , Perelli Robin M , Parker Lauren , Prange Lyndsey , Kim Jeffrey J , Howard Taylor S , Reyes Valenzuela Gabriel , Caraballo Roberto , Garone Giacomo , Vigevano Federico , Weckhuysen Sarah , Millevert Charissa , Troncoso Monica , Matamala Mario , Balestrini Simona , Sisodiya Sanjay , Poole Josephine , Zucca Claudio , Panagiotakaki Eleni , Tchaicha Sébile , Sauquet Julie , Zawadzka Marta , Mazurkiewicz-Beldzinska Maria , Fons Carmen , Anticona Jennifer , De Grandis Elisa , Groppa Sergiu , Paryjas Sandra , Megvinov Andrey , VAVASSORI ROSARIA , Landstrom Andrew P
Published: June 2023

Introduction:
Variants in the
ATP1A3
-encoded sodium-potassium ATPase-3 can result in Alternating Hemiplegia of Childhood (AHC), which was previously believed to primarily be a neurologic disease. Patients with
ATP1A3
variants can experience sudden unexplained death (SUD) which has been linked with cardiac arrhythmias. Given that pathogenic variants in
ATP1A3
are rare, the goal was to conduct a multicenter study to determine the impact of
ATP1A3
variants on cardiac repolarization and lethal arrhythmia predisposition.

Methods:
This study was conducted by members of the International AHC Research Consortium (IAHCRC) according to the collaboration rules defined in the IAHCRC Charter. We analyzed 12-lead electrocardiograms from 134 patients from 12 centers across 7 countries. Of these patients, 120 had variants in
ATP1A3
. Patients were grouped as follows:
ATP1A3
variant status (positive vs. negative) and variant frequency (D801N vs. E815K vs. G947R vs. other). Blinded, manual measurements of QT intervals and QTc calculations were performed by 2 pediatric electrophysiologists. The Gollob criteria was used to establish an abnormally short QTc measurement of <370 ms.

Results:
QTcs were significantly shorter when comparing
ATP1A3
variant positive patients to negative (
P
=0.004). Patients with the
ATP1A3
-D801N variant had significantly shorter QTcs compared to E815K, G947R, and all other less common variants (
P
=0.0105,
P
=0.0234,
P
=0.0076, respectively).
ATP1A3
-D801N variant average QTc was 363.9 ms and remained <380 ms throughout adulthood for 68% of this population. Of the 34 patients with the
ATP1A3
-D801N variant, 23 had short QTcs and 3 of those patients had ventricular tachycardia/ventricular fibrillation arrest, cardiac death, or an ICD implanted for exercise-induced syncope.

Conclusions:
In the largest study to date of the impact of
ATP1A3
variants on the heart, we find that patients with
ATP1A3
-D801N variants have shorter QTcs and are more likely to experience arrhythmias, which can cause syncope and even sudden death. The shortened QTc, which is a predisposing factor for the generation of ventricular arrhythmias, may underlie the SUD etiology in patients with AHC. Patients with variants in
ATP1A3
should receive regular cardiac evaluation.
Abstract 15040: Atrial Arrhythmia Burden and Mortality in Patients With Congenitally Corrected Transposition of The Great Arteries (ccTGA)
Authors: Chiriac Anca , Jaideep Bhalla , Espinosa Samantha , Umadat Goyal , Gonzalez Carolyn , Phillips Sabrina D , Asirvatham Samuel , Madhavan Malini , McLeod Christopher J
Published: June 2023

Background:
Patients with ccTGA have a high incidence of atrial arrhythmias and premature failure of the systemic right ventricle. We sought to better define this risk.

Methods:
A retrospective review of all clinical data for patients with ccTGA followed at a large tertiary care institution was performed. The primary outcome was a composite of death and cardiac transplantation.

Results:
A cohort of 165 patients (age 41±16 years, 53% male) were followed for 11±8 years; 41 patients died, 7 underwent cardiac transplantation, and 4 underwent VAD placement. Male sex (HR 2.7, p=0.002), older age (HR 1.04, p<0.001), clinical heart failure symptoms (HR 7, p<0.001), heart failure hospitalization (HR 4.9, p<0.001), syncope (HR 1.8, p=0.04) and pulmonary hypertension (HR 2.77, p<0.001) were significant predictors of the primary outcome. Atrial fibrillation (HR 3.5, p=0.002), atrial flutter (HR 3.05, p=0.04), and prolonged QRS duration (HR 1.01, p=0.004) on the first ECG, as well as right and left atrial enlargement (HR 4, p<0.001 and 3.7, p<0.003) and severe systemic AV valve regurgitation (HR 3.8, p=0.03) on the first echocardiogram were associated with poor outcomes.

Atrial arrhythmias occurred in 110(67%) patients: atrial fibrillation in 75(45%), atrial flutter in 50(30%), and supraventricular tachycardia in 16(9.7%) patients. Arrhythmias were largely asymptomatic in 109(66%) patients, while 25(14.5%) experienced palpitations, dizziness or presyncope, and 10(6%) presented with decompensated heart failure. Cardioversion and antiarrhythmic therapy were utilized in 53(32%) patients. Surgical pulmonary vein isolation or atrial MAZE were performed in 15(9%) patients, cryoablation of the CTI in 3 patients, and surgical ablation of an accessory pathway in 2 patients. One or more catheter ablation procedures were also performed in 18(11%) patients.

Conclusions:
Atrial fibrillation and flutter, heart failure, prolonged QRS duration, systemic AV valve regurgitation and pulmonary hypertension predict worse outcomes in ccTGA. Although asymptomatic in a majority of patients, atrial arrhythmias are associated with significant morbidity and mortality. Whether a rhythm control strategy even in asymptomatic patients may improve outcomes remains unknown.
Abstract 15060: New Diagnostic Method Using Latest Spectral Computed Tomography With Dual-Layer Detector to Diagnose Pulmonary Thromboembolism and Pulmonary Infarcted Tissue Changes
Authors: Funabashi Nobusada , Misumi Kazuo
Published: June 2023

Introduction:
Spectral CT with a dual-layer detector generates CT images at any keV (range: 40-200) after ordinary acquisition using virtual monoenergetic settings (VMS). An appropriate keV improves the contrast of a pulmonary artery (PA) thrombus (PAT). On iodine no water (INW) display, areas with decreased PA blood flow are visualized. With effective atomic number display (Z effective), infarcted and normal lung tissues are distinguished.

Hypothesis:
Spectral CT improves the detection of PAT, areas with decreased PA blood flow, and infarcted lung tissue, increasing diagnostic accuracy.

Methods:
We performed enhanced 128 slice Spectral CT 7500 (Philips) scans with a dual-layer detector in 23 patients (11 males, 61±13 years) with clinically suspected PAT. VMS images at various keV values were created from spectral-based images. We developed an INW display to detect decrements in PA blood flow and also made Z effective displays to distinguish infarcted from normal lung tissue. We measured patent PA lumens, PAT, lung areas with decrements in PA flow and infarcted lung tissue.

Results:
19 patients had PAT. Of the remaining 4 patients, two revealed decrements in PA flow on INW display and lung tissue changes on Z effective display. On a spectral profile analysis using images in the early phases using contrast, lower keV values were associated with markedly and slightly increased mean CT values for the patent PA lumen and PAT, respectively. Lower keV values were associated with markedly increased mean CT values for normal lung tissue, however, mean CT values were constant at various keV values for an area related to decrements in PA blood flow by INW display and also infarcted lung tissue by Z profile, simultaneously, respectively (Figure).

Conclusions:
A small PAT may be missed in enhanced CT. However, spectral CT can detect PAT, an area corresponding to decrements in PA blood flow on INW display, and also distinguish infarcted from normal lung tissue on a Z profile, simultaneously.
Abstract 15077: Reconnection of Pulmonary Veins and Left Atrial Posterior Wall Following Catheter Ablation for Atrial Fibrillation in Real-World Patients: Registry Data From a High-Volume Center
Authors: Mohanty Sanghamitra , Shetty Sai Shishir , Baho Karim , Asfour Issa , Della Rocca Domenico G , QUINTERO MAYEDO ANGEL , MacDonald Bryan , Gianni Carola , Morris Trevor , Kessler Danielle , Bassiouny Mohamed , Gallinghouse G , Burkhardt John , Horton Rodney , Al-Ahmad Amin , Di Biase Luigi , Di Biase Luigi , Natale Andrea
Published: June 2023

Introduction:
Durable isolation of the pulmonary veins (PV) and the left atrial posterior wall (LAPW) are considered as key determinants of long-term success after catheter ablation in AF patients. Objective: We aimed to evaluate the PV and LAPW reconnection rate in real-world patients undergoing redo-ablation at our center.

Methods:
Consecutive AF patients that underwent their first AF ablation at our center from 2015-19 were included in this analysis. At the index procedure, all received electrical isolation of PVs and the LAPW area between the PVs, using radiofrequency (RF) ablation. Procedure was conducted with 3.5-mm irrigated-tip catheter guided by circular mapping catheter, intra-cardiac echocardiography and a 3-D mapping system. RF energy was delivered with a maximum temperature setting of 42
0
C, contact force of 10g and a power of up to 45W. Posterior wall isolation was performed using multiple ablation points covering the whole posterior wall. An esophageal probe was utilized in all patients to monitor esophageal temperature during ablation in the LAPW in close proximity to the esophagus. Complete abolition of all PV potentials rather than decrease in the amplitudes was the end point and confirmed by entrance and/or exit block. All patients were followed up prospectively for 2 years with quarterly evaluation during the first year and bi-annually afterwards and the data was collected in our IRB-approved AF registry. Recovery of conduction in the PVs and LAPW were assessed at the redo procedure using pacing or incremental isoproterenol infusion of 20- 30μg/min for 15-20min.

Results:
During the study period, 6,817 AF ablation procedures were performed at our institution of which 3,113 AF patients undergoing their first catheter ablation were included in the analysis and prospectively followed up for 2 years. Baseline characteristics of the study population is given in Table 1. At 23.1±12.8 months of follow-up, 614 (19.7%) patients had received redo-ablation, of which 139 (22.6%) had one or more PV or LAPW reconnected.

Conclusion:
In this series, with experienced operators performing the procedures, the rate of recovery of conduction in the PVs and LAPW was low compared to the reported high incidence rate in the literature.
Abstract 15082: Altered Functional Brain Circuitry in Fetuses With Complex Congenital Heart Disease
Authors: Cruz Josepheen D , Kapse Kushal , Lopez Catherine , Vezina Gilbert , Donofrio Mary T , Wessel David L , du Plessis Adre , Limperopoulos Catherine
Published: June 2023

Recent reports describing regional alterations involving critical hubs of the developing brain have emerged in neonates with complex CHD prior to surgery. However, the extent to which postnatal brain connectivity disturbances reflect a prenatal onset of aberrant functional circuitry development is unknown. Here, we investigated whether neural connectivity changes are present in fetuses with CHD before birth. We acquired 176 resting state scans from 156 pregnant women who were prospectively enrolled. We analyzed 76 scans from 61 CHD fetuses (mean±sd:33.4±3.1 gestational weeks, GW); which included transposition of the great arteries, n=22; hypoplastic left heart syndrome, n=20; other CHD, n=34) and 103 scans from 95 healthy controls (33.8±3.3 GW). First, we defined 98 anatomic regions (

nodes

) using a fetal atlas. Next, for each fetus, we computed connectivity – the pairwise Fisher-
z
transformed Pearson correlation, (
z(r)
) – across all 98 nodes. Only the strongest 4% of connections, or 190

edges

, were included. Next, we grouped nodes into 16 clusters, or

modules

, based on a node’s connectivity to other nodes. We then compared (1) the number of connections within (

w-edges

) and between (

b-edges

) modules, and (2) the strength of connectivity within (

w-strength

) and between (

b-strength

) modules. We expected 12/190 w-edges and 177/190 b-edges but observed 55 and 54 w-edges in healthy (H) and CHD fetuses, respectively, 4.5x greater than the expected. Thus, in both cohorts, the normalized w-edges were significantly greater than the normalized b-edges (
p
< 0.001); there were no significant between-group differences. However, w-strength (H,1.16±0.26; CHD, 1.14±0.31) and b-strength (H, 1.05±0.19; CHD, 1.04±0.26) were significantly reduced in CHD (
p
<0.001). In both, w-strength was greater than b-strength (p<0.001). For the first time, we demonstrated that CHD functional networks follow normative trajectories where within-module connectivity predominates, both in strength and number, in-utero. Fetal CHD connectivity strength, however, was weaker compared to controls suggesting that altered functional brain circuitry in CHD has its origins in-utero. Further studies are needed to assess the surveillance and prognostic potential of these findings.
Abstract 15094: Inflammatory Genotype-Phenotype Interaction Moderates Response to a Cardiovascular Disease Risk Reduction Intervention in Rural Adults at-Risk for Cardiovascular Disease
Authors: Key Kaitlin V , Moser Debra K , Morford Lorri A , Lennie Terry , Rayens Mary Kay , Biddle Martha J , Mudd Martin Gia
Published: June 2023

Introduction:
Systemic inflammation and inflammatory genotypes have been associated with cardiovascular disease (CVD) risk, with associations between C-reactive protein (CRP), a marker of systemic inflammation, the rs1205 polymorphism on the
CRP
gene, and CVD risk among the most well-studied. However, little is known about the effect of systemic inflammation and associated genotypes on response to CVD risk reducing interventions. The purpose of this study was to examine whether high sensitivity C-reactive protein (hsCRP) moderated the association between rs1205 genotype and response to a CVD lifestyle-focused risk-reduction intervention.

Methods:
Participants were 400 rural adults with 2+ CVD risk factors participating in the
HeartHealth in Rural Kentucky
study. At baseline, we measured serum hsCRP and genotyped participants for the rs1205 polymorphism. Genotypes were categorized as CC or CT/TT. Response to the
HeartHealth
intervention was estimated by the pre-to-post intervention percent change in Framingham Risk Score (FRS). A moderation analysis with subsequent floodlight analysis was conducted using PROCESS macro for SPSS. Analyses were adjusted for body mass index, education, financial status, marital status, and insurance status.

Results:
Participants were aged 51.2±13.3 years and predominantly female (73.6%). The rs1205 genotype’s effect on FRS change was moderated by hsCRP (p=.004). Subsequent floodlight analysis revealed that rs1205 genotype had a larger effect on FRS change among those with lower (<0.54 mg/L; p=.05) and higher (>7.67 mg/L; p=.05) hsCRP as compared to those with hsCRP ranging from 0.54-7.67 mg/L (p >.05). Among those with lower hsCRP, those with the CC genotype had a larger decrease in FRS than those with CT/TT genotypes. Among those with high hsCRP, those with the CT/TT genotypes experienced a larger decrease in FRS to those with the CC genotype.

Conclusion:
Findings suggest that inflammatory phenotype moderates the relationship between inflammatory genotype and response to a CVD risk reduction intervention. This highlights the need to examine additional inflammatory markers and inflammatory genotypes to determine the impact of inflammation and genetics on responsiveness to CVD risk reduction interventions.
Abstract 15106: Impaired Regional Strain by Cardiovascular Magnetic Resonance Feature-Tracking Predicts Low Sensing Value After Cardiac Defibrillator Implantation in Patients With Arrhythmogenic Cardiomyopathy
Authors: Chen Zhongli , Song Yanyan , Chen Liang , Zhao Shihua , Chen Keping
Published: June 2023

Introduction:
Inadequate ventricular sensing at implantable cardiac defibrillator (ICD) implantation in patients with arrhythmogenic cardiomyopathy (ACM) is troubling and might cause inappropriate ICD interventions and complications. We aimed to evaluate the value of ventricular mechanics features in predicting low sensing value by emerging cardiovascular magnetic resonance-feature tracking (CMR-FT) in ACM patients.

Hypothesis:
CMR-FT characteristics prior to ICD implantation might assist in predicting low R wave amplitude.

Methods:
We retrospectively enrolled ACM patients receiving CMR examinations prior to ICD implantation at our center from January 2011 to July 2021. The strain parameters of LV and RV were analyzed by CMR-FT. The R wave amplitude (RWA) was obtained within 24 hours of completion of the ICD implantation and its association with CMR strain parameters was analyzed.
Results:
We enrolled 83 ACM patients with a median RWA of 8.0 mV (Interquartile range IQR:5.4-12.1 mV) and impedance within the normal range. 18 (21.7%) patients were found with low RWA (<5mV) despite attempts in over 5 positions. RV strain parameters including RV global longitudinal, circumferential and radial strain rather than LV strain parameters correlated significantly with RWA (Spearman’s correlation coefficients: GLS: -0.35, GCS: -0.58, GRS: 0.59, all P<0.01). RVGRS and RVGCS were found not only associated with RWA after adjusting for clinical cofounders (coefficients: RVGCS: -0.53, RVGRS:0.32, p<0.01) but also valuable in predicting low RWA (areas under the curve: 0.76 and 0.73 respectively; sensitivity: both 0.72, specificity: both 0.71).

Conclusions:
Low sensing of ICD lead in ACM patients was associated with impaired RV mechanics. RVGCS and RVGRS by CMR-FT were valuable parameters for predicting low RWA and might assist operation planning.
Abstract 15112: Subcutaneous versus Transvenous Implantable Defibrillator Recipients: A Systematic Review and Meta-Analysis
Authors: Saleem Maryam , arshad verda , Nabavizadeh Pooneh , Alhasan Faysal , Do Duc H , Rizwan Afzal Muhammad , Weiss Raul , Costea Alexandru
Published: June 2023

Introduction:
Subcutaneous implantable cardioverter-defibrillator (S-ICD) is an alternative to transvenous implantable cardioverter-defibrillator (T-ICD) in select patients with complex anatomy, high infection risk and venous access issues. T-ICD is known to cause perioperative and long-term complications. Considering expanding indications for S-ICD, ongoing uncertainty in efficacy and unknown utility in low-risk patients, we performed this updated meta-analysis to study device related complications in both the systems.

Methods:
We performed a meta-analysis using electronic literature search to retrieve studies that compared S-ICD to T-ICD. Outcomes of interest were efficacy and device-related complications. Outcomes were pooled under random-effects and reported as risk ratios (RRs) and 95% CIs. 15 studies (observational, case-control and RCTs), median follow up 31.1 months, with variable heterogeneity for different outcomes (Fig-1), were included to capture real-world data.

Results:
A total of 21628 patients (S-ICD group n=3594, male 72.6%, mean age 50.1±10y and T-ICD group n=18034, male =72.6%, mean age 53.3±10.6y) were recruited. Lead-related complications were significantly lower in S-ICD, RR {0.21 [0.13, 0.34], P=<0.00001}. There were no significant difference in other device-related endpoints: 30-day complications RR{0.67 [0.38, 1.18], P=0.17}; surgical complications RR{0.70 [0.49, 1.01], P=<0.05}, inappropriate therapy RR{ 0.85 [0.67, 1.07], P=0.16}; appropriate therapy RR{ 0.62 [0.35, 1.09], P=0.10}, infections requiring surgery RR {0.84 [0.44, 1.59], P=0.59} and all-cause mortality RR{0.91 [0.68, 1.2, P=0.52].

Conclusion:
Efficacy and safety of S-ICD is non-inferior to T-ICD and superior for lead-related complications.
Abstract 15114: Estimation of Left Ventricular Filling Pressure Using Left Atrial Strain in Coarctation of Aorta
Authors: ABOZIED OMAR , Goda Ahmed , Ramachandran Dhanya , Andi Kartik , Egbe Alexander C
Published: June 2023

Background:
Left atrial (LA) reservoir strain <18% and booster strain <8% have been proposed as the optimal threshold to detect increased left ventricular (LV) filling pressure in patients with acquired heart disease. This study aimed to determine whether these LA strain cut-off points can detect increased LV filling pressure in adults with coarctation of aorta (COA).

Methods:
Retrospective study of adults with COA (n=126; age 36±16 years), that underwent non-simultaneous cardiac catheterization and echocardiography. Increased LV filling pressure was defined as pulmonary artery wedge pressure (PAWP) >12 mmHg or LV end-diastolic pressure (LVEDP) >16 mmHg.

Results:
The median PAWP was 13 (11-18) mmHg, and had a good correlation with LA reservoir strain (r=-0.69, p<0.001) and LA booster strain (r=-0.61, p<0.001). LA reservoir strain <18% had superior diagnostic power to detect PAWP >12 mmHg as compared to LA volume index >34 ml/m2, septal E/e’ >15, lateral E/e’ >13, and tricuspid regurgitation velocity >2.8 m/s (p<0.05 for all). The median LVEDP was 17 (14-20) mmHg, and LVEDP had a modest correlation with LA reservoir strain (r=-0.39, p<0.001) and LA booster strain (r=-0.33, p=0.002). LA reservoir strain <18% had superior diagnostic power to detect LVEDP >16 mmHg as compared to LA volume index >34 ml/m2, septal E/e’ >15, lateral E/e’ >13 and tricuspid regurgitation >2.8 m/s (p<0.05 for all).

Conclusions:
These data suggest that LA strain could be used to identify patients with increased LV filling pressure thereby improving patient selection for cardiac catheterization and interventions.
Abstract 15124: Impact of Stable Coronary Artery Disease on In-Hospital Outcomes and Readmissions Following Catheter Ablation for Atrial Fibrillation
Authors: Satish Mohan , Walters Ryan , Alla Venkata , Halperin Jonathan L
Published: June 2023

Introduction:
Outcomes within coronary artery disease (CAD) patients after catheter ablation (CA) for atrial fibrillation (AF) remain unclear. In this study, we assessed the impact of stable CAD on 90-day readmission rates following hospitalization for CA of AF.

Methods:
Using the Nationwide Readmissions Database (NRD), we identified all hospitalizations from the fourth quarter of 2015 to 2019 with a Medicare Severity-Diagnosis Related Group for a percutaneous intracardiac procedure, a procedure code for CA, and a primary discharge diagnosis of AF. Presence of acute coronary syndrome (ACS) at index hospitalization was excluded to define stable CAD and stratify by its presence. Our primary outcome was all-cause 90-day readmission; secondary outcomes included readmission for AF, repeat CA, ACS, and heart failure (HF). We controlled for selection bias using inverse probability of treatment weights (IPTW) and targeted the average treatment effect.

Results:
An estimated 28,466 hospitalizations for CA for AF were identified, of which 3,171 (11.1%) had concomitant stable CAD. Of note, no index hospitalization included a HF diagnosis, regardless of stable CAD. The 90-day all-cause readmission rate was significantly higher in patients with stable CAD compared to those without stable CAD (18.4% vs. 14.4%, p = .006; Fig. 1) with a significantly higher burden of new ACS (5.3% vs. 1.1%, p < .001) and new HF (17.0% vs. 10.2%, p = .007). AF recurrence rates as 90-day readmission did not differ statistically (21.9% vs. 26.5%, p = .217). Further pooled analysis of all 90-day HF readmissions revealed a significantly higher burden of older patients, with underlying chronic kidney or pulmonary disease, and persistent and chronic AF subtypes.

Conclusions:
Our large-scale analysis suggests that in patients hospitalized for CA for AF, stable CAD is a marker for adverse prognosis and is associated with a higher 90-day readmission rate and significant burden of new ACS and new HF.
Abstract 15140: Post-Myocardial Infarction Ventricular Septal Defect in a Patient With Mixed Connective Tissue Disorder
Authors: Gardy Adam , Lima Gian , Sargeant Jarred
Published: June 2023

Mixed connective tissue disorder (MCTD) is associated with a broad range of cardiovascular abnormalities, including coronary artery disease (CAD). It has been proposed that chronic systemic inflammation plays a key role in the development of atherosclerotic disease.

A 66-year-old female with a history of MCTD and hypertension presented with mild dyspnea and pleuritic chest pain after one week of persistent flu-like symptoms. Her blood pressure was 108/77 mmHg, pulse 92 bpm, saturating 98% on room air. She was comfortable and denied other risk factors such as diabetes, hyperlipidemia, or prior smoking history. On exam she was found to have a soft holosystolic murmur across her precordium. EKG showed sinus rhythm with small Q waves and ST elevation in V1-V6. She was taken for cardiac catheterization which revealed a thrombotic occlusion in the proximal left anterior descending artery (LAD) and a severe lesion in the left circumflex artery. She underwent angioplasty with one drug eluted stent placed to LAD. Left ventriculography revealed a VSD near the apex, and transthoracic echocardiogram showed a 7.6 mm muscular VSD with left to right shunt, ejection fraction of 35% and hypokinesis of the anterior wall. She became hypotensive and required vasopressors prior to coronary artery bypass grafting and primary closure of her apical VSD. Intraoperatively, a 2 cm VSD with 5 cm of necrotic surrounding tissue was noted. Post-operative complications included asystolic cardiac arrest, marked cardiogenic shock and multiorgan failure to which she ultimately succumbed.

Post-myocardial infarction VSD is a rare complication of MI occurring in approximately 0.2% of cases. However, patients with MCTD can develop atypical symptoms, resulting in delayed presentation and therefore higher risk of mechanical complications. We highlight the importance of a thorough physical exam and high suspicion for mechanical complications in these patients even when hemodynamically stable.
Abstract 15141: Machine Learning-Driven Serum Metabolomics: Insights Into the Transition to Early-Stage Heart Failure With Preserved Ejection Fraction
Authors: Alborghetti Marcos Rodrigo , Hortegal Renato , Pereira Jose , Grizante Mariana , Cancellier Renato , Fernando Giolo Alves Luiz , Valeri de Freitas Renata , Moretto Carnielli Carolina , Sforca Mauricio , Moriya Henrique Takachi , Paes Leme Adriana , Feres Fausto , Franchini Kleber
Published: June 2023

Introduction:
Metabolomics has emerged as a powerful tool in providing readouts of early disease states before clinical manifestation. Here we used the predictive power of Unsupervised Hierarchical Clustering Analysis (UHCA) and Automated Machine Learning (AutoML) algorithms to identify serum metabolic panels in a population at risk of developing HFpEF.

Methods:
We studied 215 subjects staged as non-HF, pre-HFpEF and early-stage HFpEF(es-HFpEF). We evaluated clinical, laboratory, echocardiographic, and NMR-based metabolomics of blood serum data. UHCA and AutoML were used to explore metabolic fingerprints potentially related to clinical features or HFpEF. We used Metabolite Set Enrichment Analysis to explore biochemical pathways.

Results:
The UHCA identified three major patients (P) and two metabolites (M) clusters (Figure). The P clusters were associated with HFpEF stages, cardiac remodeling, diastolic dysfunction, and sex (Pearson Chi-square, p < 0.05) and M clusters with glycine and serine metabolism and urea cycle pathways (FDR-adjusted p-value < 0.002). Considering non-HFpEF and es-HFpEF groups, AUROC mean for feature subset combinations was 0.897 and the highest AUROC (0.995) combined metabolites, clinical, laboratory and echo features. Of the 64 models trained that included metabolites as input, serine (25), uridine (17), 2-oxoglutarate (14), citrate (14), 2-aminobutyrate (13) and taurine (13) were observed more frequently with feature importance value greater than zero. The metabolites with higher sum values of feature importance were serine (0.173), uridine (0.131), 2-aminobutyrate (0.123), choline (0.098) and dimethylamine (0.087).

Conclusions:
This study revealed characteristic metabolite profiles in the sera of patients at risk of developing HFpEF. These metabolite panels can add information for classificatory algorithms development and contribute to the understanding of HFpEF pathophysiology.
Abstract 15151: Identification of Novel Right Ventricular Function Phenotypes in Pulmonary Arterial Hypertension Using Unbiased K-Means Clustering
Authors: Vanderpool Rebecca R , Janowski Alexandra M , Fauvel Charles , Liu Zilu , Lin Shili , Correa-Jaque Priscilla , Webb Amy , Kanwar Manreet , Kraisangka Jidapa , Mathur Puneet , Perer Adam , Everett Allen D , Visovatti Scott H , Benza Raymond L
Published: June 2023

Introduction:
Survival in pulmonary arterial hypertension (PAH) is associated with right ventricular (RV) function rather than pulmonary vascular resistance (PVR). At present, RV function is not incorporated in current risk assessment models and studies evaluating RV function are generally limited to single-center studies. The aim was to identify novel RV function phenotypes using unbiased k-means clustering in patients with PAH.

Methods:
Baseline clinical and hemodynamic data in patients with PAH were harmonized data from 5 PAH clinical trials (COMPASS3: n=98, EARLY: n=176, GRIPHON: n=720, MAESTRO: n=44, and SERAPHIN: n=728). Pearson correlation analysis was used to select variables that reduce the co-linearity (|r| < 0.7) between hemodynamic variables used in the models. K-means clustering methods were applied to advanced RV hemodynamics including end-systolic pressure (ESP), arterial elastance (Ea), single-beat end-diastolic elastance (Eed), Pulse pressure (PP), stroke volume (SV) and RV stroke work (RVSW). Survival analysis was used to compare all-cause mortality among each cluster group.

Results:
Participants in the harmonized dataset (n=1766) had a mean PAP of 53 ± 17 mmHg, a cardiac output of 4.3±1.4 L/min, a wedge pressure of 9±4 mmHg and a PVR of 11.8±7.4 WU. K-means clustering identified four distinct RV cluster phenotypes that range from mild to severe RV dysfunction (Fig. A). Participants in RV cluster 1 (RV C1) have severe RV dysfunction with increased pressure/afterload, decreased cardiac function, and increased diastolic stiffness compared to RV cluster 4 (RV C4). (Fig. A) RV C1 had decreased six-minute walk distance compared to other clusters. RVC1 and RVC2 had increased risk of mortality compared to RV C4 (Fig. B).

Conclusion:
Applying K-means clustering to harmonized hemodynamic data from PAH clinical trial data identified 4 unique RV function phenotypes with different clinical outcomes.
Abstract 15156: Statistical Modeling of Cardiac-Derived Progenitor Cell Extracellular Vesicles to Predict Clinical Trial Outcomes
Authors: Hoffman Jessica R , Park Hyun-Ji , Bheri Sruti , Davis Michael E
Published: June 2023

Introduction:
Cardiac-derived c-kit+ progenitor cells (CPCs) are under investigation in the CHILD phase I clinical trial (NCT03406884) for the treatment of hypoplastic left heart syndrome (HLHS). Therapeutic efficacy of CPCs can be attributed to the release of extracellular vesicles (EVs), carrying beneficial RNA cargo. Despite some successes with pediatric cardiac cell therapy, large variation in cell populations and patient outcomes remains a problem. To investigate these discrepancies and understand sources of cell therapy variability we took a machine learning approach: combining bulk CPC-derived EV (CPC-EV) RNA sequencing and cardiac-relevant
in vitro
experiments to build a predictive model.

Methods:
We isolated CPCs from cardiac biopsies of congenital heart disease patients (n=30) and the lead-in HLHS patients in the CHILD trial (n=7). We cultured CPCs, collected EVs from the media, and sequenced EV miRNA and total RNA. We treated cardiac endothelial cells and fibroblasts with CPC-EVs and measured inflammatory or fibrotic gene expression with qRT-PCR. We treated mesenchymal stromal cells with CPC-EVs and assessed migration in a Boyden chamber system. We treated cardiac endothelial cells seeded on Matrigel with CPC-EVs and measured tube formation. Finally, we put together the CPC-EV sequencing and experimental data in partial least squares and regularized regression models.

Results:
With our models we determined that the most important CPC-EV RNA signals involved in pro-reparative outcomes had significant fit to cardiac development and signaling pathways. Furthermore, using a model trained on previously collected CPC-EVs, we were able to predict
in vitro
outcomes for the CHILD clinical samples. Finally, we formed rank-based predictions for the CHILD lead-in patients, based on the
in vitro
assays.

Conclusions:
The CHILD phase I trial is set to conclude next year. We will validate our predictions with the release of these clinical data. With this work, we (1) investigated the EV RNA signals involved in pediatric cardiac repair and (2) will use our
in vitro
results to predict CHILD clinical trial outcomes. Our results highlight the importance of quantitative studies in determining the underlying variance in pediatric cardiac cell therapy.