bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15620: Diagnostic Accuracy of Virtual Non-Contrast CT for Aortic Valve Stenosis Severity Evaluation
Authors: Lorenzatti Daniel A , Feinberg Ari , Pina Santana Pamela , Daich Jonathan , Perez-Cervera Javier , Miranda Rita , Halliburton Sandra , Schenone Aldo L , Scotti Andrea , Kuno Toshiki , Dey Damini , Pibarot Philippe , Dweck Marc R , Garcia Mario J , Slipczuk Leandro
Published: December 2023

Introduction:
Computed tomography (CT) aortic valve calcium (AVC) score has important prognostic and diagnostic value in patients with aortic stenosis, especially in those evaluated for TAVR, but at the expense of an additional non-contrast scan. Dual-energy CT (DECT) allows virtual non-contrast reconstructions (VNC) from conventional contrast acquisitions.

Aims:
Compare the diagnostic performance of VNC-AVC score as compared to TNC-AVC score for identifying severe AS.

Methods:
We prospectively included patients undergoing pre-TAVR CT with a DECT system (IQon, Philips). TNC-AVC score was acquired using a prospective acquisition and VNC-AVC score derived from a contrast-enhanced retrospective scan. Both scores were calculated using the Agatston method. A correction proportionality constant was applied. Concordant severe AS was defined as AVA<1cm2 and either Vmax >4cm/s or mean gradient ≥40mmHg. Spearman, Cohen’s Kappa, and Bland-Altman were used to assess concordance.

Results:
In total, 109 patients were included: mean age of 79 ± 10 yrs, 55% female, 43% with concordant severe, 43% LF-LG, and 14% moderate AS. TNC scan median radiation was 116 mGy*cm (IQR 53-366). The median TNC-AVC was 2753 AU (1652-4135), while the median VNC-AVC was 1900 AU (946-2752) after applying the constant (1.43). A strong correlation was demonstrated between methods (r=0.89; p<0.001; Figure). Using accepted thresholds (>1300 AU for women and >2000 AU for men), 68% (n=74) of patients had severe AS by TNC. After estimating thresholds for VNC (>660 for women and >1519 for men), 60% (n=65) had severe AS, demonstrating substantial agreement with TNC-AVC (K;=0.71). Among individuals diagnosed with LF-LG, 38% and 34% exhibited severe AS by TNC/VNC, respectively, and only 12% and 11% in those with moderate AS.

Conclusions:
DECT-derived VNC-AVC demonstrates substantial agreement with TNC AVC, without requiring an additional scan and reducing both radiation exposure and acquisition time.
Abstract 15639: An Explainable Machine Learning-Based Phenomapping Strategy for Adaptive Predictive Enrichment in Randomized Controlled Trials of Preventive Interventions
Authors: Oikonomou Evangelos K , Thangaraj Phyllis M , Bhatt Deepak L , Ross Joseph S , Young Lawrence H , Krumholz Harlan M , Suchard Marc A , Khera Rohan
Published: December 2023

Introduction:
Randomized controlled trials (RCT) are the cornerstone of evidence-based preventive cardiovascular care but are resource intensive. We propose a novel machine learning (ML) strategy of adaptive predictive enrichment through computational trial phenomaps to optimize RCT efficiency.

Methods:
In simulated group sequential analyses of two cardiovascular outcomes RCTs of (1) a drug (pioglitazone vs placebo; IRIS), and (2) a management strategy (intensive vs standard blood pressure reduction; SPRINT), we constructed dynamic phenomaps to infer patient profiles benefiting from the intervention vs control during interim analyses. We examined their ability to adaptively enrich subsequent trial enrollment. We compared the final study size and effect estimates between the adaptive and original study designs.

Results:
Across 3 interim analyses, our strategy learned dynamic signatures of individualized benefit. By conditioning prospective participant enrollment on dynamic estimates of personalized benefit, our approach enabled a robust reduction in the trial size across simulations (-18% ± 4.7% in IRIS, p=0.008 [
A
] and -27.4% ± 3.4% in SPRINT, p=0.002 [
B
]), also preserving the original average treatment effect (IRIS: hazard ratio of 0.71 ± 0.01 for pioglitazone vs placebo; vs 0.76 in the original trial [
C
]; SPRINT: hazard ratio of 0.72 ± 0.01 for intensive vs standard systolic blood pressure; vs 0.75 in the original trial; all p<0.01 [
D
]). Hierarchical assessment of safety endpoints revealed no safety concerns with adaptive enrichment, whereas post-hoc review of the enriched populations confirmed that no specific demographic groups were excluded from the analysis.

Conclusions:
We present an explainable ML algorithm for adaptive predictive enrichment in RCTs leveraging phenome-wide computational measures of personalized benefit. These findings propose a new paradigm to maximize clinical trial efficiency through dynamic data-driven inference.
Abstract 15642: Discrimination Against Physicians in Interventional Cardiology
Authors: Rempakos Athanasios , Alexandrou Michaella , Simsek Bahadir , Kostantinis Spyridon , Karacsonyi Judit A , Mutlu Deniz , Hall Allison , Seto Arnold , Danek Barbara A , Shah Binita , Baechler Courtney , Thomas Delaine , Choi James , Rier Jeremy , Kearney Kathleen , Park Ki , Bennett Mosi , Garcia Santiago A , Duong Thao , Kerrigan Jimmy , Al-ogaili Ahmed , Rangan Bavana V , Mastrodemos Olga , Allana Salman S , Sandoval Yader , Burke M Nicholas , Brilakis Emmanouil S
Published: December 2023

Background:
Data on discrimination against physicians in the field of interventional cardiology are limited.

Methods:
We performed an online, anonymous, international survey of interventional cardiologists.

Results:
A total of 445 interventional cardiologists participated in the survey. Median age was 46-50 years and most (61%) practice in the United States. Among the participants, 13% were women and 13% belonged to underrepresented minority groups. Participants were asked to discern which characteristics contribute to discrimination against physicians in their workplace. Several characteristics were identified (Figure): language accent (48%), race/ethnicity (44%), age (44%), gender (43%), and appearance/clothing (40%). Women were more likely to have experienced discrimination by patients and families (81% vs 54%; p<0.001), peers (81% vs 45%; p<0.001), supervisors (73% vs 43%; p<0.001), support staff (64% vs 36%; p<0.001), and nursing staff (63% vs 37%; p=0.001), compared with men. Similarly, among participants who practice in the US, UK, Canada, and Australia (n=296), physicians whose first language was not English were more likely to have experienced discrimination from patients and families (73% vs 46%; p<0.001), peers (63% vs 35%; p<0.001), supervisors (56% vs 33%; p<0.001), support staff (51% vs 28%; p<0. 001), and nursing staff (52% vs 31%; p=0.001), compared with native English speakers. Both women (60% vs 7%; p<0.001) and underrepresented minority groups (28% vs 12%; p=0.003) were more likely to be mistaken for a non-physician employee, compared with men and non-underrepresented minority groups respectively. While 9% (n=42) of the total participants reported incidents of discrimination to their respective organizations, only 19% of those (n=8) expressed satisfaction with the response received.

Conclusions:
Our survey provides a snapshot of the current status of discrimination faced by interventional cardiologists.
Abstract 15647: Patient Perceptions of Cardiac Rehabilitation and an Adjunct Mobile Application: A Qualitative Analysis
Authors: Gupta Prerna , Waughtal Joy , Martinez Monica , Chavez Catia , Finer Elijah , Gutierrez-Raghunath Silvia , Khazanie Prateeti , Ho Michael , Bull Sheana , Peterson Pamela
Published: December 2023

Background:
Cardiac rehabilitation (CR) is underutilized despite demonstrated improvement to quality of life and mortality for patients with cardiovascular disease (CVD) patients. As a part of an ongoing study among an underserved urban population to improve participation in CR alongside a mobile application (app) to encourage healthful habits, we assessed CR and app perceptions among participants.

Methods:
We conducted in-depth open-ended interviews with a sample of patients with low socioeconomic status at Denver Health, an urban safety-net hospital with generally racially and ethnically diverse patients. We transcribed interviews and performed content analysis to identify themes. Study staff trained in qualitative methods interviewed patients on thevia phone with the goal of understanding their perceptions of CR and app use. We transcribed interviews and performed content analysis to identify themes.

Results:
Among 19 interviews (6 female), all patients enjoyed CR, especially the interaction with CR staff. Four patients self-identified as non-app users (1 female) vs. 15 users (5 female). Users were aged 55 years old (SD 10.4) on average, versus 66.5 years old (SD 3.4 years) among non-users. Overall 18/19 interviewees were below the poverty line in Denver for a single income household (Table). Non-users expressed reluctance around technology, and one could not recall training on app use by research study staff though they had generally higher educational status. Users identified communication with CR staff via the app as the most useful feature.

Conclusion:
Overall, patients liked CR, and most identified themselves as app users. Users appreciated education about healthy diet, and the ability to interact with CR staff. App users were surprisingly of lower educational status, but similar income backgrounds. This may suggest that older users among a vulnerable population require more support in accessing mobile interventions despite educational status.
Abstract 15656: Early Recurrence of Ventricular Tachycardia and the Impact of Radiofrequency Ablation on Success of ICD Therapy
Authors: Giedrimiene Dalia , Alvarez Chikezie , Tolat Aneesh , Fakess Seth , Kluger Jeffrey
Published: December 2023

The early success of radiofrequency ablation (RFA) and impact on ICD delivered therapy (including the need for antitachycardia pacing (ATP) or ICD shock) after the procedure, due to recurrent VT events, is still not clear.

Hypothesis:
Recurrences of VT during 12 months of follow up (FU) after RFA are associated with the need for ICD therapy (successful ATP or need for ICD shock) and related to pre-procedural ATP success or failure.

Methods:
We analyzed the data of 141 ventricular arrhythmia patients who underwent RFA during 2019 - 2022 by identifying 54 (38.3%) patients with monomorphic VT and implanted ICDs. Age - 69.54±10.04 years
,
52 (96.3%) males, BMI - 29.1±6.2; 27 (50.0%) patients - ICM; 51 (94.4%) used antiarrhythmics and 40 (82.1%) have failed; beta-blockers use - 47 (87.0%). 20 (37.0%) had an ICD for primary prevention. LVEF - 39.2±13.8%, VT cycle - 350±80 ms. VT storm - in 46 (85.2%).

Results:
Out of 54 included patients, only 34 (63%) had no recurrent VT events during FU post-RFA procedure. 20 (37.0%) experienced recurrent VT events and needed ICD therapy: 8 (40.0%) responded to ATP, whereas 12 (60.0%) failed ATP and required an ICD shock. Patients’ response to ICD delivered therapy was compared between two groups of patients: 1) pre-ablation ATP failure (n=40) and 2) pre-ablation ATP success (n=14). In pre-ablation ATP failure group, 23 (57.5%) patients had no recurrent VT events, 5 (12.5%) successfully responded to ATP and 11 (27.5%) failed ATP requiring ICD shock. In the pre-ablation ATP success group, 9 (64.5%) patients had no recurrent VT, 3 (21.4%) responded to ATP, and only 1 (7.14%) required ICD shock and no VT storm episodes, whereas 12 (30%) of patients with pre-procedural ATP failure had VT storm (IQR= 0.0, 0.0, vs 1.0, 5.0 respectively; p=0.019). Patients with recurrent VT events had higher BMI then patients with no recurrent VT: 32.9±5.4 vs 28.0±6.0, p< 0.033. The pre-ablation ATP failure group had a greater proportion of hemodynamically unstable VT induced during RFA (56.7% vs 23.1%; p=0.043).

Conclusion:
The success of ATP after RFA was associated with pre-procedural ATP response and patients with lower BMI had less recurrent VT events. Overall, pre-ablation ATP failure for VT termination may identify patients with increased risk of failure to ATP therapy.
Abstract 15657: Stroke Survivors’ and Caregivers’ Experience of Using Game-Based Virtual Reality Training Modules Designed for Promoting Social Participation
Authors: Lo Suzanne H , Chau Janita P , Choi Kai Chow , Lau Alexander Y , Lee Vivian W , Kwok Chi Fai Eddie C , David Thompson , Zhang Robin Tianjiao T
Published: December 2023

Introduction:
Virtual reality (VR) technology may provide a promising alternative to promote stroke survivors’ social participation. Three innovative social participation-focused, game-based VR training modules for community-dwelling stroke survivors were developed.

Aim:
This study sought to understand the survivors’ and caregivers’ perceptions of the usefulness of VR-based interventions in supporting post-stroke recovery and their experience of using the specially developed VR modules.

Methods:
A qualitative study with semi-structured, in-depth, individual interviews was conducted with a convenience sample of 10 stroke survivor-caregiver dyads (n=20). Each survivor and caregiver attended a first interview about their perceptions and expectations of VR-based interventions. They were then invited to experience all games of the VR modules and were interviewed again about their experience and satisfaction with using the VR modules, and suggestions on areas for improvement. All interview data were transcribed verbatim and analyzed thematically.

Results:
Most of the survivors (mean age=60.80; SD=6.71) were female (70%), had an ischemic stroke (50%), and walked with a stick (70%). The mean years after stroke was 4.80 (SD=4.16). Most of the caregivers were female (80%) and had a mean age of 56.20 years (SD=7.73). All survivors had no prior VR experience. Three themes were identified: A modern strategy instilling enjoyment into the regular physical training; confidence boosting for reengaging into life situations and outdoor activities; and tailored modifications needed for reviewing training progress, supporting more social interactions and controller-free experience. They suggested enabling availability of the modules in survivors’ home or community settings for increasing the convenience to access the modules.

Conclusions:
The findings showed that the new VR training modules are acceptable to the survivors. Feedback elicited informed refinement of the modules and the usefulness of the modules in improving social participation of survivors will be evaluated in a large-scale randomized controlled trial.
Abstract 15665: Lack of Association Between Inpatient Percutaneous Coronary Intervention Volume and Thirty-Day Readmissions After Acute Myocardial Infarction- Cardiogenic Shock
Authors: Bansal Kannu , Gupta Mohak , Garg Mohil , Patel Neel , Vallabhajosyula Saraschandra
Published: December 2023

Introduction:
Volume-outcome relationship data is limited for acute myocardial infarction-cardiogenic shock (AMI-CS). Revascularization is mainstay of therapy in AMI-CS.

Objectives:
Authors sought to examine relation between hospital inpatient percutaneous coronary intervention (PCI) volume and 30-day readmissions after an AMI-CS admission.

Methods:
Nationwide Readmissions Database (NRD) 2016-2019 was analyzed. Hospitals were categorized into quartiles (Q1, lowest to Q4, highest) based on annual inpatient PCI volume. Primary outcome of interest was 30-day unplanned all-cause readmissions. Secondary outcomes included cardiac, non-cardiac and heart-failure (HF) readmissions at 30-days.

Results:
A total of 49,558 index AMI-CS admissions were present in 3,954 PCI performing hospitals. Median hospital PCI volume was 174 (inter-quartile range 70-316). 59% admissions for AMI-CS were present in quartile Q4. Overall, 30-day readmission rate was 18.5% (n=9,179); of which 56.2% were cardiac, 43.8% were non-cardiac and 25.8% were related to HF. We did not find any difference in 30-day all-cause readmissions (Q1 = 17.6% vs. Q2 = 18.4% vs. Q3 = 18.2% vs. Q4 = 18.7%, p=0.55). Similarly, cardiac (Q1 = 10.9% vs. Q2 = 11.0% vs. Q3 = 10.6% vs. Q4 = 10.2%, p=0.29), and HF (Q1 = 5.0% vs. Q2 = 4.8% vs. Q3 = 4.8% vs. Q4 = 4.8%, p=0.99) readmissions were not different across quartiles. Non-cardiac readmissions were more-commonly observed in higher quartiles (Q1 = 6.7% vs. Q2 = 7.4% vs. Q3 = 7.7% vs. Q4 = 8.5%, p=0.001). However, no significance was noted with any outcome after multivariable adjustment. Similarly, no relationship was observed between hospital PCI volume as continuous variable and all-cause or cause-specific readmissions on restricted cubic spline analysis.

Conclusions:
In a national representative sample of 3,954 hospitals with 49,558 AMI-CS admissions, we found lack of an association between hospital PCI volume and 30-day all cause or cause-specific readmissions.
Abstract 15673: Evaluation of the Use of Wearable Device Signals for Patients With Heart Failure: A Subgroup Analysis in the Michigan Predictive Activity & Clinical Trajectories in Health (MIPACT) Study
Authors: Pastapur Aishwarya , Pescatore Nicole , Shah Nirav , Kheterpal Sachin , Nallamothu Brahmajee K , Golbus Jessica R
Published: December 2023

Background:
Wearable devices are increasingly used by patients and the data made available to their care teams. However, interpretation of these data, especially in diverse populations, remains challenging. Herein, we report on the results of a subgroup analysis of wearable device data among participants with heart failure (HF) within a large observational digital health study.

Methods:
The MIPACT Study enrolled 6765 adult Michigan Medicine patients with an iPhone 6 or newer between August 2018 and December 2019. All were provided with an Apple Watch. The electronic medical record was reviewed to determine New York Heart Association (NYHA) functional class and HF phenotype. Wearable activity data (e.g., step count, exercise minutes) were compared across phenotypes and functional classes using a one-way ANOVA.

Results:
118 participants had an ICD-10 code for HF within 90 days of enrollment and were confirmed to have HF on chart review. Participants were 57.4 (SD 14.2) years of age; 68 (57.6 %) were male and 29 (24.6%) Black. 29 (26.9%) participants had NYHA class 2 and 10 (8.5%) NYHA class 3 symptoms; 35 (29.9%) had HF with preserved EF (HFpEF) and 85 (81%) nonischemic cardiomyopathy. Participants with NYHA class 1 HF symptoms had significantly higher mean daily exercise minutes and mean daily step counts when compared to patients with NYHA class 2 HF symptoms and with a composite of NYHA classes 2-4 (Figure 1). Participants with HF with mildly reduced EF (HFmrEF) had significantly higher exercise minutes and step counts when compared with participants with HFpEF and HF with reduced EF (HFrEF). Participants with HFrEF and HFpEF were similar with respect to exercise minutes (p = 0.82) and step counts (p = 0.91).

Conclusion:
Wearable physical activity measures vary by HF phenotype and functional classification with similar profiles for patients with HFpEF and HFrEF. Further research is necessary to understand longitudinal changes in wearable device signals and prognosis.
Abstract 15684: Adherence and Persistence to SGLT2 Inhibitors in Patients With Heart Failure
Authors: Kono Shogo , Moon Jungyeon , Chong Alice , Fang Jiming , Ko Dennis T , Austin Peter , Atzema Clare , Naimark David , Udell Jacob A , Stukel Therese , Tu Karen , Booth Gillian , Jackevicius Cynthia
Published: December 2023

Introduction:
While originally used solely as antihyperglycemic agents, sodium-glucose cotransporter 2 inhibitors (SGLT2i) are now recommended for use in heart failure (HF) to reduce hospitalization and cardiovascular mortality. Unfortunately, benefits of treatment can only be fully realized if a patient is adherent to therapy. While SGLT2i adherence has been found to be suboptimal in diabetes populations, SGLT2i adherence has not been well-studied in patients with HF. Since medication non-adherence in HF tends to be high in general, and can lead to worse clinical outcomes, this study aimed to estimate SGLT2i adherence/persistence rates in a population-based cohort of HF patients.

Methods:
This retrospective cohort study included patients ≥65 years discharged alive from a hospital in Ontario, Canada between 4/2016 and 3/2021, who had a primary diagnosis of HF and were dispensed a SGLT2i prescription. Prescription claims were used to identify and calculate 6-month and 1-year SGLT2i adherence and 1-year persistence, from the first date of fill for an SGLT2i. Adherence was calculated as the proportion of days covered (PDC), with PDC≥80% defined as “good” adherence. Persistence was calculated with a “permissible” gap of 30 days allowed before being considered non-persistent. A cumulative incidence function was utilized to account for the competing risk of death in persistence calculations.

Results:
There were 5,257 eligible patients (59% male, mean age 76.94±7 years, 73.8% with diabetes), for whom empagliflozin (64.9%), dapagliflozin (25.5%) and canagliflozin (9.5%) were used. The overall mean PDC was 83.9% at 6-months and 80.5% at 1-year, with the proportion of patients with “good” adherence (PDC≥80%) at 76.2% and 72.5%, respectively. Persistence to all prescribed SGLT2i was 71.3% at 1-year, with highest persistence with dapagliflozin at 74.4% and lowest persistence with canagliflozin at 68.1% [p=0.01].

Conclusion:
In this HF cohort on SGLT2i, nearly 3 out of 4 patients were highly adherent and persistent at one year. SGLT2i adherence/persistence rates are higher than seen in studies in diabetes populations. Further studies are needed to identify those at risk of non-adherence/non-persistence and to examine association with clinical outcomes.
Abstract 15692: Clinical Outcomes in TAVR Patients Receiving Oral Anticoagulation Stratified by Baseline Creatinine Clearance Levels: A Subanalysis of the ENVISAGE-TAVI AF Trial
Authors: Mehran Roxana , Nicolas Johny , Chen Cathy , Hengstenberg Christian , Jin James , KIMURA TETSUYA , Laeis Petra , Unverdorben Martin , Van Mieghem Nicolas , Zamorano Jose , Dangas George
Published: December 2023

Introduction:
The ENVISAGE-TAVI AF (NCT02943785) trial compared edoxaban (EDO) vs vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) after successful transcatheter aortic valve replacement (TAVR). The effect of baseline creatinine clearance (CrCl) on efficacy and safety of EDO vs VKA in these patients is not well understood.

Hypothesis:
The efficacy and safety of EDO vs VKA in patients with AF undergoing TAVR will vary across the range of baseline CrCl.

Methods:
In this post-hoc analysis from the ENVISAGE-TAVI AF trial, we stratified patients by oral anticoagulation (OAC) strategy (EDO vs VKA) and CrCl (CrCl ≥90 mL/min, CrCl 60-89 mL/min, CrCl 45-59 mL/min, CrCl 30-44 mL/min, CrCl ≤29 mL/min).

Results:
Of 1426 patients included, 46.3% (n = 676) had CrCl from 60 to 89 mL/min. Patients with lower CrCl trended older in age than those with higher CrCl (
Table 1
). The annualized event rates for all outcomes tended to increase with decreasing CrCl (
Table 2
). Across the range of CrCl, patients receiving EDO vs VKA had higher rates of major bleeding and major gastrointestinal bleeding but lower rates of non-cardiovascular death. Major bleeding did not translate into increased all-cause death. Rates of intracranial hemorrhage were higher with EDO vs VKA in patients with CrCl ≥90 mL/min but lower in all other patients. For all-cause death, differences between EDO and VKA were numerical and did not reach statistical significance.

Conclusions:
In this ENVISAGE-TAVI AF subanalysis, decrements of CrCl appeared to correlate with rates of adverse outcome parameters more than OAC strategy. Due to low event rates in some outcomes, these results should be interpreted with caution.
Abstract 15696: Simultaneous Presentation of ST-Elevation Myocardial Infarction, Ischemic Stroke, and Pulmonary Embolism in a Patient With Thrombus-in-Transit Across a Patent Foramen Ovale
Authors: Petrella Richard W , Martz Colin , Kaneko Tsuyoshi , Bach Richard G
Published: December 2023

Case Description:
A 70-year-old woman with a history of hypertension, hypothyroidism, and sigmoid colectomy, presented to the ER with altered mental status, slurred speech, and left-sided weakness. She was hemodynamically stable, and exam was notable for dysarthria, left-sided facial droop, and left-sided upper and lower extremity weakness. ECG showed ST-elevation in leads I, aVL, and V1-V3, and ST-depression in II, III, and aVF. CT Head was without intracranial hemorrhage. Emergency coronary angiography showed subtotal thrombotic occlusion of the left main, LAD, and LCX arteries consistent with embolic etiology. Coronary thrombectomy re-established TIMI 3 flow. The patient then underwent CTA of the head and neck, which visualized both right anterior M2 occlusion and large pulmonary emboli in the right and left main PAs. She underwent emergency mechanical thrombectomy of the right MCA. With induction of anesthesia she suffered PEA arrest, for which she received 5 minutes of CPR and epinephrine and ROSC was obtained. She then underwent successful thrombectomy of the right anterior M2. Patient then underwent bilateral pulmonary thrombectomy and IVC filter placement. Over the ensuing 24 hours she weaned from pressors, was extubated, and was alert with only mild left hemiparesis. Bilateral lower extremity venous dopplers were negative for DVT, and an echocardiogram showed a serpiginous echodensity in both atria and across the intra-atrial septum, consistent with a large thrombus-in-transit through a PFO. CT Surgery was consulted, and patient underwent successful bi-atrial thrombectomy with PFO closure.

Discussion:
Simultaneous thromboembolic MI, stroke and PE is an exceedingly rare and catastrophic clinical presentation. Initial management should involve a promptly-assembled multidisciplinary team to determine if the patient is a candidate for procedural or operative intervention, and, if so, to determine the order in which they should be completed. Subsequently, a workup should be initiated to determine an underlying cause of the presentation, including appropriate thrombophilia workup and imaging. If feasible, surgical thrombectomy and PFO closure may be indicated to prevent further embolic phenomena.
Abstract 15706: Common- and Rare-Variant Genetic Architecture of Heart Failure Across the Allele Frequency Spectrum
Authors: Lee David S , Depaolo John , Aragam Krishna , Biddinger Kiran , Conery Mitchell , Dikilitas Ozan , Khan Atlas , Puckelwartz Megan , Reza Nosheen , Satterfield Benjamin A , Arany Zoltan , Cappola Thomas P , Day Sharlene , Joseph Jacob , McNally Elizabeth M , Owens Anjali T , Voight Benjamin F , Levin Michael , Damrauer Scott M
Published: December 2023

Background:
Heart failure (HF) is a complex trait influenced by environmental and genetic factors. Genome-wide association studies (GWAS) have found common genetic variants associated with HF risk, but the extent that common and rare variants explain risk and implicate similar genes and pathways in HF remains less understood.

Methods:
For common variants, we meta-analyze existing GWAS of all-cause HF with data from the Million Veteran Program, including 207,346 individuals with HF and 2,151,210 without in diverse populations. We examine rare coding variants in the Penn Medicine BioBank (PMBB) using gene-collapsing association studies and burden heritability regression. We test for an interaction between a polygenic risk score (PRS) based on our GWAS meta-analysis and truncating variants in
TTN
(TTNtv).

Results:
GWAS meta-analysis identified 176 risk loci (146 previously unreported), implicating known risk factors for HF and genes involved in cardiac development. New signals at
GIPR/
GLP1R highlight potential contributions of dysregulated glucose homeostasis and metabolism in HF. Gene collapsing studies identified associations between HF and rare loss-of-function variants in
TTN
(OR 2.94, 95% CI 2.43-3.56) and
MYBPC3
(OR 7.71, 95% CI 3.97-14.97) at exome-wide significance. HF heritability mediated through common variants (4.5%) was significantly higher than for rare variants (1.8%), but rare variant heritability was further enriched in cardiomyopathy genes compared to common variants (27-fold vs. 3.4-fold). We found a significant interaction between a new multi-ancestry HF-associated PRS (AUC 0.72, 95% CI 0.72-0.73) and TTNtv carrier status (interaction OR 1.32, 95% CI 1.06-1.64).

Conclusions:
Common and rare variants contribute to HF heritability. Common variant HF heritability is highly polygenic, while rare variant burden heritability appears more concentrated in core cardiomyopathy genes. HF risk conferred by TTNtv carrier status is further increased by an individual’s polygenic contribution. Our results support the continued inclusion of cardiomyopathy genes in rare-variant genetic testing panels for HF but suggest a meaningful polygenic component to HF exists that is not currently captured by clinical genetic testing.
Abstract 15722: Developing a Patient-Centered Roadmap to Reduce Maternal Morbidity/Mortality for Individuals With Congenital Heart Disease
Authors: Messmer Mindi , Leezer Scott , Phillippi Ruth , ROEDER MARK , Russo Melissa , Fries Melissa , Cribbs Marc , John Anitha
Published: December 2023

Background:
Individuals with congenital heart disease (CHD) face higher rates of pregnancy-related complications and interventions, however, few studies have assessed ways to improve outcomes.
Goal:
Improve reproductive care and reduce maternal morbidity and mortality for pregnant individuals with CHD.

Methods:
We formed a diverse consortium of CHD patients, providers, and advocates to identify knowledge deficits. Survey responses were solicited through social media and professional and advocacy networks.

Results:
As of 6/2/23, respondents included 815 (11% male, 88% female) patients from 48 states DC, and 216 providers (19% male, 81% female). Providers included 90 (42%) midwives, 59 (28%) adult congenital cardiologists, and 41 (19%) maternal-fetal medicine specialists. Most patient respondents are CHD patients (n=781, 96%) with complex CHD anatomy (n=606, 81%) between the ages of 30 and 44 (52%) with 72% reporting an annual household income over $75,000. Some patients reported they had received contraception counseling (n=262); counseling was provided by a physician (n=149, 57%), registered nurse (n=37, 14%), or parent (n=36, 14%). Of 189 CHD patients, the top reasons cited for not pursuing a pregnancy included not being ready (n=80, 42%), concerns about their heart condition (n=78, 41%), and physician advice due to potential complications (n=59, 31%). More than half of the patient respondents (n=231, 51%) reported a pregnancy, and 147 (64%) reported their pregnancy caused stress and anxiety. Cost and provider education are top priorities for improving care for pregnant individuals with CHD for respondents with household incomes under $49,000 per year while access to specialized heart care and obstetrics are top priorities for those with incomes over $50,000 (see Figure 1).

Conclusions:
CHD patients and providers are eager to provide their experiences relating to pregnancy and patient-centered research is an important tool to bridge the knowledge gap.
Abstract 15750: Impact of Acute Heart Failure on COVID -19 Patients: An Insight From Nationwide Inpatient Sample
Authors: Manasrah Nouraldeen , Atti Lalitsiri , Duhan Sanchit , Ali Shafaqat , Micho Tarec , Titus Anoop , Pandya Krutarth K , Patel Neel N , sattar yasar , AlJaroudi Wael , Alraies M Chadi C
Published: December 2023

Introduction:
Patients with COVID-19 had experienced adverse cardiovascular outcomes, such as myocarditis, MI, and Heart Failure (HF). Among them, HF has emerged as the most common critical complication during COVID-19 exacerbations, potentially leading to increased mortality rates and poorer clinical outcomes. However, there is a lack of available data to thoroughly investigate the consequences of acute HF in patients admitted with COVID-19.

Methods:
We analyzed the Nationwide Inpatient Sample (NIS) dataset to select COVID-19 patients over 18 years old who were hospitalized during 2020, in the United States (US) using ICD-10. Based on the presence of acute HF, patients were divided into two cohorts. Propensity score was used to match patients across various factors including age, race, sex, and comorbidities.

Results:
A total of 1,666,960 COVID-19 patients were hospitalized in 2020, of which 156,755 (9.4%) had associated HF. COVID-19 patients with HF had a mean age of (72.38±13.50) years compared to (62.3 ± 17.67) years for patients without HF. HF patients had a higher prevalence of HTN, hyperlipidemia, type 2 diabetes, smoking, and preexisting cardiovascular disease. After propensity matching, HF patients had higher rates of in-hospital mortality (23.86% vs 17.63%, p<0.001), acute MI (18.83% vs 10.91%, p<0.001), acute stroke (0.78% vs 0.58%, p=0.004), cardiogenic shock (2.56% vs 0.69%, p<0.001), and sudden cardiac arrest (5.54% vs 3.41%, p<0.001) compared to those without HF.

Conclusions:
COVID-19 patients admitted with acute HF had worse clinical outcomes and higher mortality rates. In addition to a higher length of stay and healthcare compared with patients without HF.
Abstract 15760: A Critical Contribution of Cardiac Myofibroblasts and a Predictive Role of UCP2 SNPs in the RV Decompensation in Pulmonary Hypertension
Authors: Zhang Yongneng , Lorenzana Carrillo Maria A , Tejay Saymon , Haromy Alois S , Liu Yongsheng , Zhao Yuan Yuan , Sutendra Gopinath , Michelakis Evangelos D
Published: December 2023

Introduction/hypothesis:
The mechanism driving the transition from compensated (cRVH) to decompensated right ventricular hypertrophy (dRVH) in pulmonary hypertension (PHT) is unknown. We hypothesized that a transition from cardiac fibroblasts (cFB) to cardiac myofibroblasts (cMFB) underlies this mechanism. Decreased mitochondrial calcium (mCa
++
) promotes cMFB differentiation (from cFB). Methylation of mCa
++
uptake 1 (MICU1) and lack of UCP2 (uncoupling protein 2, a component of the mCa
++
uniporter complex) decrease mCa
++
, and therefore, activity of Krebs enzymes that produce diffusible metabolites, regulating epigenetic mechanisms that drive change in cell identity.

Methods/Results:
In the monocrotaline-rat PHT model, we separated cRVH from dRVH based on strict hemodynamics (canulating the main pulmonary artery through the jugular vein) and Echo: dRVH had decreased cardiac output, increased right atrium pressure, decreased TAPSE and increased RV end diastolic diameter compared to cRVH. In isolated hearts, RV systolic pressure was lower in dRVH but in isolated cardiomyocytes (CM), contractility (sarcomere shortening) was not, pointing to a non-cardiomyocyte difference. The number of cMFB was not different between cRVH and Control, but dramatically increased in dRVH. Mitochondrial respiration was lower in dRVH cMFB than cRVH cFB. mCa
++
was progressively decreased from Control to cRVH to dRVH c(M)FB, while it was not different in CM. The MICU1 methyltransferase (PRMT1) levels and methylation of immunoprecipitated MICU1 were increased but the expression of UCP2 was decreased from Control to cRVH to dRVH c(M)FB (but not CM). In human RV tissues (from autopsy or biopsy, n=15), dRVH had increased number of cMFB compared to Control and cRVH. Cytoplasmic PRMT1 was increased and UCP2 was decreased from Control to cRVH to dRVH c(M)FB. In a cohort of 25 patients with PHT that had Echo and right heart Cath within 48 hours, carriers of the loss-of-function UCP2 SNP (rs659366) had decreased TAPSE compared to non-carriers that had similar mean PA pressure.

Conclusion:
A change of cell identity (cFB to cMFB) in the RV may be the basis of cRVH to dRVH transition, rather than contractile failure of CM. UCP2 SNP may predict early dRVH, if confirmed in larger cohorts.
Abstract 15763: Increasing Diversity Among Research Participants Through Patient Engagement in the Congenital Heart Initiative
Authors: Messmer Mindi , Leezer Scott , Jackson Jamie L , Papneja Shreya , Asghar Areeba , Phillippi Ruth , marlin aliza , ROEDER MARK , Hile Danielle , Agarwal Anushree , Lewis Matthew J , Saidi Arwa , Kanter Ronald J , Sandhu Satinder K , YOUNG THOMAS W , Jacobsen Roni , Ruckdeschel Emily , Lubert Adam M , Singh Harsimran , Zaidi Ali N , Halpern Dan , mathews anita , Timmons Susan , Carton Thomas , John Anitha S
Published: December 2023

Background:
The Congenital Heart Initiative (CHI) is the first patient-powered digital registry for adults with congenital heart disease (ACHD). The CHI-Redefining Outcomes and Navigation to Adult-Centered Care (CHI-RON) study is built upon the CHI as a unique collaboration with PCORnet.

Goal:
Recruitment of populations that are racially diverse, younger, out-of-care, and male has been challenging in ACHD studies. Our goal was to design patient engagement and recruitment strategies to increase these underrepresented populations.

Methods:
Launched in December 2020, patients across the globe can self-enroll in the CHI registry. The CHI-RON study, initiated in May 2022, recruits ACHD patients at 12 PCORnet centers. Patients are involved in all aspects of the study including recruitment (see Figure 1).

Results:
As of May 2023, a total of 2,520 participants were recruited by CHI-RON centers while 1,494 self-enrolled in the CHI. Most participants report complex CHD anatomy (n=1,660, 49%). A total of 762 (36%) participants are considered out of care. CHI-RON recruitment methodologies increased representation when compared to self-enrolled CHI participants in terms of ethnicity (10.3 % vs 7.4% Hispanic, p=0.005), race (5.4% vs 2.6%, African American, p<0.001), sex (41% vs 28% male, p<0.001), age (34.8 +/-12.5 years vs 44.5 +/- 14.3 years, p<0.001), and education (33% vs 22% high school equivalent or less, p<0.001). Most patients involved in the study team (n=11, 83%) reported a very to extremely high degree of meaningfulness (average score 85.2) per the Patient Engagement in Research Scale (PEIRS-22). The mean scores of each of the seven subdomains demonstrated significant meaningfulness, especially in the subdomains of convenience, contributions, and benefits.

Conclusions:
Patient engagement is critical to improving the inclusion of underrepresented populations in clinical research and ensuring alignment with the needs of ACHD patients.
Abstract 15769: Ventricular Interdependent Phenotype of CPC-Pulmonary Hypertension With Normal Left Atrium and Pericardial Restraint: Impact on CPET Metrics and Clinical Outcomes
Authors: Zampierollo-Jaramillo Giovanna , Abed Anas , Tu Wanxin , Garcia-Arango Mariana , ElShaer Ahmed , Heffernan Shannon , Esmaeeli Amir , Runo James , Masri Sofia , Raza Farhan
Published: December 2023

Background:
Combined pre- and post-capillary pulmonary hypertension (Cpc-PH) has overlapping pathophysiology due to left heart disease and pulmonary vascular disease, which may vary in an individual patient.

Hypothesis:
While the majority of CpcPH patients have left heart disease with abnormal left atrium, a minority of CpcPH patients have normal left atrium and develop elevated left-sided pressures due to exaggerated ventricular interdependence and pericardial restraint.

Aim:
to define ventricular interdependent sub-phenotype of CpcPH.

Methods:
30 CpcPH patients undergoing invasive cardiopulmonary exercise test with complete echocardiographic data were identified. Abnormal left atrium group was defined as left atrial volume index ≥40mL/m
2
and E/E' ≥10, and rest was defined as normal left atrium group. p-value <0.05*

Results:
Key metrics of abnormal (n=23) vs normal (n=7) left atrium subjects are shown in Figure. In the same order (abnormal vs normal), age was 65±15 vs 61±16, female gender 6 (26%) vs 4 (57%), BMI 34±8 vs 38±10, H2FpEF score 5.8±2.3 vs 5.3±1.7, BNP 514±406 vs 191±280, eccentricity index 1.12±0.25 vs 1.24±0.38, RV:LV ratio 0.9±0.3 vs 0.9±0.2, E' medial 5.6±1.7 vs 9.7±4.0*, E' lateral 6.8±2.2 vs 9.2±1.9*, TAPSE/PASP 0.33±0.12 vs 0.41±0.18, epicardial fat 6±2 vs 6±3, delta ETCO
2
-1.9±2.0 vs +1.7±2.1. Rest hemodynamics: mPAP 42±6 vs 37±11, PAWP 21±3 vs 18±3*, CO 4.9±1.4 vs 5.4±0.8, PVR 4.6±2.2 vs 3.4±1.5. With exercise: mPAP/CO slope 9.2±6.5 vs 6.1±4.5 and PVR 3.8±2.5 vs 2.7±1.2. Comorbidity burden between the two groups did not have a statistically significant difference. On one-year follow-up, incidence of mortality and heart failure hospitalizations were: 16 (69%) vs 1 (14%)*.

Conclusions:
A subset of CpcPH with normal left atrium have increased pericardial restraint and lower left ventricular transmural pressure. This likely leads to LV compression and Cpc-PH physiology. This sub-cohort has better exercise capacity and clinical outcomes.
Abstract 15771: Cardiosphere-Derived Cell Extracellular Vesicles (CDC-EVs) Alter C-C Chemokine Receptor Type 2 (CCR2) Mediated Monocyte Pro-Inflammatory Signaling Following Cardiac Injury
Authors: Tarvirdizadeh Touba , Pandey Rohan , Mentkowski Kyle I , Schiffmacher Paul , Eagler Lisa , Reynolds Jessica , Lang Jennifer K
Published: December 2023

Background:
Following cardiac damage, CCL2 (a cytokine released by the injured cardiac tissue) recruits CCR2+ monocytes to the site of injury. Heightened CCL2 levels, however, can over activate the CCR2+ mediated pro-inflammatory response leading to poor cardiac healing. Cardiosphere-derived cell extracellular vesicles (CDC-EVs) have been shown to suppress the inflammatory response by decreasing CCR2 monocyte expression. We hypothesized that treatment with CDC-EVs would suppress CCR2 expression of peripheral monocyte in patients with acute MI.

Methods:
A prospective single arm observational study was performed. Inpatients at Buffalo General Medical Center were recruited following these criteria: 1) >18 years of age AND 2) a type I MI. Subjects were excluded for the following: 1) fever in last 2 days/infection, 2) is or may be pregnant, or 3) currently undergoing cancer treatment. Monocytes were isolated from peripheral blood samples using Ficoll/centrifugation followed by magnetic activated cell sorting. Isolated monocytes were incubated with either PBS, normal human dermal fibroblast EVs (NHDF-EVs) or CDC-EVs. Monocytes then were analyzed for CCR2 expression by flow cytometry. Multi-variate analysis was performed.

Results:
CDC-EVs significantly reduced classical monocyte expression of CCR2 by 23% as quantified by flow cytometry compared with PBS (p<0.05, one way ANOVA, n=23) and by 13% compared with NHDF-EVs (p<0.05, one way ANOVA, n=23) in patients with recent MI. This reduction was seen regardless of patients’ pre-existing co-morbidities, medications, LVEF, or history of PCI. Smoking was associated with decreased response to CDC-EV mediated CCR2 suppression (Linear regression model R -0.93, p<0.05, n=23).

Conclusions:
CDC-EVs effectively downregulate CCR2 expression in patients with recent MI, representing a potential adjunct to current clinical therapies in patients with a heightened pro-inflammatory response post-MI.
Abstract 15777: Vascular Density and Fibrosis in Heart Failure Recovery
Authors: Ranka Rajul K , Youker Keith A , Bhimaraj Arvind , Cooke John P
Published: December 2023

Introduction:
Chronic unloading with a left ventricular assist device (LVAD) leads to LV remodeling including increased endothelial density, reduction of fibrosis, and improved cardiac function. Specific mechanisms of such recovery have not been fully explored in humans. Hypothesis: We hypothesize that recovery from non-ischemic heart failure is accompanied by increased vascular density and reduction in fibrosis.

Methods:
We developed and characterized a murine model of non-ischemic heart failure (HF) and recovery (HFR) using Angiotensin II infusion pumps and L-NAME/NaCl in water for 5 weeks followed by removal of these insults to induce a recovery. Ejection fraction, LV mass, fibrosis, and vessel density were assessed at various time points. We quantified vessel density using fluorescent microsphere bead perfusion and measured fibrosis using Masson’s Trichrome staining. Statistical analysis was performed using One way ANOVA, n=5 mice/group with 2 replicate experiments. (
p
<0.05 was considered significant.)Results: LV mass and interstitial fibrosis increased significantly while ejection fraction and vascular density showed significant decreases in HF vs control mice while recovering hearts showed normalized ejection fraction and LV mass with a significant reduction in fibrosis. There was a very significant increase in vascular density when compared to HF mice (Fig. 1). Together, these preliminary data support our hypothesis that recovery from heart failure involves a vascular recovery.

Conclusions:
Morphological recovery of cardiac function is accompanied by an increase in vascular density along with a reduction in fibrosis in a non-ischemic mouse model of heart failure recovery. This increase in vascular density may be a required component of the recovery process from heart failure and further studies are necessary to understand the specifics of such mechanisms.
Abstract 15813: Machine Learning Improves Prediction of Heart Failure and Cardiovascular Death Through a Signal Analytical Approach of Echocardiography
Authors: Simonsen Jakob O , Hoejlund Rune , Modin Daniel , Skaarup Kristoffer G , Christensen Jacob , Lassen Mats , Johansen Niklas D , Sanchez Sergio , Claggett Brian , Marott Jacob , Thorsten Magnus , Jensen Gorm , Schnohhr Peter , Mogelvang Rasmus , Biering-Srensen Tor
Published: December 2023

Introduction:
Recently, speckle tracking echocardiography (STE) and tissue Doppler imaging (TDI) have gained increasing traction as non-invasive tissue characterization methods within cardiology. But until now many patterns from the strain and TDI curves remain uninvestigated. Signal analytical methods like wavelet analysis have shown promising potential in effectively identifying previously unknown pathological patterns present in ECG signals. Therefore, we hypothesized that a signal analytic approach combined with supervised machine learning (ML) on strain and TDI curves could identify unknown pathophysiological deformation drivers of heart failure (HF) and cardiovascular death (CV death) in the general population.

Methods:
The analysis included 3781 subjects from the general population. In total 720 novel statistical parameters and wavelet signal parameters from 18 strain curves and 6 TDI curves were generated. The parameters were used to train an ensemble decision tree with 20-fold cross-validation and compared to a baseline ML model trained on 22 conventional echocardiographic parameters.

Results:
Follow up-time was four years. In total 108 subjects (2.9%) met the outcome. By including statistical and wavelet-derived parameters along with 22 conventional echocardiographic parameters in a combined model, the ML model was significantly improved compared to the baseline model (AUC for conventional model: 0.76 vs combined model: 0.825, p = 0.0086). Both statistical parameters, such as the mean and skewness of the TDI curve, as well as wavelet parameters, such as mean on the first decomposition level of the strain curve, were found to be important in the model.

Conclusion
Adding novel echocardiographic parameters based on signal analytical statistics and wavelet decomposition methods to preexisting conventional echocardiographic parameters significantly improved the prediction of incident HF or CV death in ML models.