bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4138850: PASCAL versus MitraClip in mitral valve transcatheter edge-to-edge repair: A systematic review and meta-analysis.
Authors: Mohamed Ahmed , Abdelaziz Ahmed , Afify Raneem , Elshahat Ahmed , Elesawy Mahmoud , Mohamed Elshafey Shams Mahmoud , Desouki Mariam , Elkhayat Ibrahim , Abdelazeem Basel , Banour Sandi
Published: November 2024

Introduction:
Mitral regurgitation is the second most common valvular heart disease, it has a high prevelance in older patients, transcatheter mitral valve edge-to-edge repair has been introduced as an alternative treatment to mitral valve surgery especially in the elderly, MitraClip is used as a standard treatment for transcatheter mitral valve edge-to-edge repair (M-TEER). PASCAL has recently been used with minimal evidence comparing both of them.

Aim:
We aimed to compare the outcomes of both device systems on mitral regurgitation residuals and clinical outcomes.

Methods:
PubMed, Scopus, WOS, and Cochrane were retrieved from inception until May 2024 for relevant clinical studies that compared PASCAL to MitraClip approaches in M-TEER procedure and reported the primary outcome of interest, which was the grade of MR at follow-up. Other reported outcomes were technical success, Death from any cause, and reintervention, Dichotomous data were analyzed using OR and 95% CI with a fixed-effect model.

Results:
Seven studies were included with a total of 1834 patients. MR ≤ 2 at discharge was less with MitraClip (RR, 0.67, 95%CI [0.45 to 1]), and MR ≤ 2 at follow-up was less with MitraClip (RR, 0.84, 95% CI [0.64 to 1.1]), MR ≤ 1 at follow up was significantly less with MitraClip (RR 0.69, [0.56 to 0.85]). However, there were no significant differences in technical success, Death from any cause, or reintervention between the two systems used.

Conclusion:
MitraClip and PASCAL are similar in procedural success, with better outcomes for PASCAL regarding Mitral regurgitation grades after the procedure. The guide to proceed with MitraClip or PASCAL should be guided by mitral valve anatomy, the etiology of MR, and device-specific features. Also, Large-volume RCTs are warranted to validate the current findings.
Abstract 4138864: Characterizing Coronary Artery Outcomes with Real World Use of Etanercept for Kawasaki Disease with Coronary Involvement
Authors: Rogers Ryan , Olson Aaron , Sagiv Eyal , Portman Michael
Published: November 2024

Background:
The Etanercept as Adjunctive Treatment for Acute Kawasaki Disease study, a phase 3 randomized placebo-controlled clinical trial, evaluated etanercept, a TNF-alpha inhibitor, as an adjunct to IVIg for Kawasaki Disease (KD). In children presenting with coronary artery (CA) aneurysm, etanercept resulted in reduction in progression of CA dilation and earlier aneurysm regression compared to placebo. Following study conclusion, our institution implemented etanercept as a first line IVIg adjunctive treatment for patients presenting with early CA aneurysm formation.

Hypothesis:
Real world use with etanercept as adjunct to IVIg in children with KD and CA aneurysm shows high patient compliance, is safe and results in early CA regression.

Methods:
We reviewed charts and echocardiograms for all children admitted to Seattle Children’s Hospital from 5/2019 to 4/2024 and treated with etanercept for KD with CA aneurysms at presentation (Z-score ≥2.5 per AHA aneurysm definition). Etanercept is injected subcutaneously at 0.8 mg/kg with IVIg at diagnosis and then with 2 repeat weekly doses at outpatient visits.

Results:
Thirty-six patients with KD and CA aneurysms received at least one dose of etanercept. Sixteen (44%) were <1 year of age, 17 (47%) were diagnosed with incomplete KD and 5 (14%) were ‘IVIg refractory.’ Four patients responded to a second IVIg dose and two patients received additional biologic agents. Thirty-two patients completed the 3-dose course of etanercept, with outpatient doses administered 6.6±1.5 days (mean±SD) and 13.5±2.3 days after the first. Seven patients had giant CA aneurysms (Z-score ≥10) requiring anticoagulation. In patients with giant aneurysms and at least 6-month follow-up, all aneurysms regressed to below the threshold for requiring anticoagulation beyond aspirin. Of 31 children with long-term follow-up echocardiograms available, 19 had complete resolution (Z-score <2.5) of CA dilation by 6 months, 22 by 1 year, and 29 by 2-year follow-up. No severe or serious adverse events were attributed to etanercept.

Conclusions:
Etanercept for KD with early CA aneurysms was delivered safely and with high compliance. CA aneurysm regression occurred in most patients with marked reduction in giant CA aneurysms by 6 months. These real-world data support the use of etanercept as an intensification therapy for preventing persistence of CA aneurysms in KD.
Abstract 4138901: Estimated Plasma Volume Status Reflected Changes In Hemodynamic Parameters On Echocardiogram After Treatment In Patients With Heart Failure With Preserved Ejection Fraction.
Authors: Iwakura Katsuomi , Tanaka Nobuaki , Okada Masato , OKAMURA ATSUNORI , Heitaro Watanabe , Seo Masahiro , Hayashi Takaharu , Yamada Takahisa , Yoshio Yasumura , Hikoso Shungo , Okada Katsuki , Nakatani Daisaku , Sotomi Yohei , Sakata Yasushi
Published: November 2024

Introduction:
Estimated plasma volume status (ePVS) is an index of changes in plasma volume and may play a significant role in the management of heart failure (HF).

Research questions:
Whether does ePVS reflect the hemodynamic changes after treatment in patients with HF?

Aims:
The aim of this study was to investigate the relationship between ePVS and changes in echocardiographic parameters after treatment in patients with HF with preserved ejection fraction (HFpEF).

Methods:
We retrospectively analyzed data from 1226 patients (81±9 years, 55.2 % female) registered in the PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) study, a multicenter registry of patients hospitalized for acute decompensated HFpEF. We collected blood samples and performed echocardiography on admission and shortly before discharge. We calculated ePVS based on the Strauss formula using hemoglobin (Hb) and hematocrit (Hct) values as 100 x [(Hb(discharge)/Hb(admission) x (1 - Hct(admission)) / (1 – Hct(discharge))] – 100 (%), and investigated the correlations between ePVS and changes in echocardiographic parameters. Patients were followed for median of 708 days (IQR 365, 1086 days) to observe all-cause death and major adverse cardiovascular events (MACE; death, HF hospitalization and stroke).

Results:
The median value of ePVS was -0.97 (IQR -1.10, -0.86), indicating successful volume reduction during hospitalization. The decrease of inferior vena cava (IVC) diameter was correlated with ePVS (p<0.0001). Whereas ePVS was not correlated with left ventricular (LV) end-systolic diameter, it was correlated with decreases in LV diastolic diameter (p=0.007), LV ejection fraction (p=0.01), time-velocity integral of LV outflow (TVI
LVO
, p<0.0001), LV mass (p=0.01) and left atrial diameter (p=0.0002). Among diastolic parameters, ePVS was correlated with decrease in E velocity (p<0.0001) and e’ velocity (p=0.002) but not with E/e’ ratio. Change in tricuspid regurgitation pressure gradient was inversely correlated with ePVS. A stepwise multivariate regression analysis revealed that ePVS was associated with changes in IVC diameter, E velocity and TVI
LVO
. A Cox proportional hazard model showed that ePVs was a predictor for both all-cause death and MACE.

Conclusion:
EPVs was correlated with changes in echocardiographic parameters relevant to hemodynamics after HF treatment and predicted prognosis in patients with HFpEF.
Abstract 4138912: Clinical outcomes of cardiac synchronization with or without an implantable cardioverter defibrillator based on pooled data from 5 clinical trials: a patient-level meta-analysis
Authors: Shadrin Ilya , Inoue Lurdes , Schmidler Gillian , MacKenzie Michael , Friedman Daniel , Abraham William , Cleland John , Curtis Anne , Gold Michael , Kutyifa Valentina , Linde Cecilia , Young James , TANG Anthony , Al-Khatib Sana
Published: November 2024

Background:
Cardiac resynchronization therapy (CRT) is a well-established therapy for patients with heart failure with reduced ejection fraction (HFrEF) and wide QRS. Whether CRT-defibrillators (CRT-D) reduce mortality more than CRT-pacemakers (CRT-P) remains controversial.

Aims:
To compare the clinical outcomes of CRT-D vs CRT-P using data from 5 landmark CRT trials, both overall and stratified by etiology of cardiomyopathy (ischemic vs non-ischemic), sex (male vs female), age (≥ 70 y/o vs < 70 y/o), and QRS morphology (IVCD, LBBB, RBBB).

Methods:
We performed a meta-analysis of patient level data from 5 prospective CRT trials (MIRACLE, REVERSE, RAFT, COMPANION and MADIT-CRT). Inclusion criteria were CRT-P vs CRT-D status (randomized comparison only in COMPANION), age ≥ 18 y/o and LVEF ≤ 35%. Exclusion criteria included secondary prevention ICD, QRS < 120ms, pacemaker upgrade, ventricular pacing indication, or missing data. Primary outcome was composite of time to heart failure hospitalization (HFH) or all-cause death. Secondary outcomes were time to HFH and death. Outcomes were analyzed using a frequentist Cox Proportional Hazards mixed effects model adjusted for 17 variables.

Results:
A total of 3407 patients met inclusion criteria. Relative to patients with CRT-P (n=843), those with CRT-D (n=2564) were of similar age (66 y/o, p=0.5), less often female (24% vs 34%, p<0.001), and more often had ischemic cardiomyopathy (59.4% vs 52.4%, p<0.001), Fig 1A. Primary outcome was similar across groups (HR 0.902 [0.752, 1.081], p=0.26), but all-cause mortality was lower with CRT-D vs CRT-P (HR 0.77 [0.603, 0.983], p=0.036), Fig 1B. Interaction analyses suggested lower all-cause mortality with CRT-D vs CRT-P in patients with non-ischemic cardiomyopathy (HR 0.502 [0.346, 0.726], p=0.0003) and patients age ≥70 y/o (HR 0.679 [0.502, 0.919], p=0.012), with significance preserved after Bonferroni correction (Fig 1B).

Conclusion:
In patients receiving CRT for HFrEF, those with CRT-D had lower all-cause mortality than patients with CRT-P, driven mainly by a lower mortality with CRT-D in older patients and those with non-ischemic cardiomyopathy. No significant interactions were noted between ICD&sex or ICD&QRS morphology.
Abstract 4138926: Results of an Employee Physical Activity Promotion Intervention within a Very Large Academic Health System
Authors: McCarthy Margaret , Xia Yuhe , Heffron Sean
Published: November 2024

Background:
Although healthcare workers may be aware of the risks of physical inactivity, their levels of physical activity (PA) are similar to those of all US adults, with less than half engaging in sufficient PA. The purpose of this health promotion was to encourage daily PA among employees in a large urban healthcare system. We also tested whether individualized progress updates further influenced PA.

Methods:
This 10-week PA program was available to all employees across all practice locations of NYU Langone Health. Employees could sync their phone or accelerometer (e.g., Fitbit) via app or web browser to count.it, the vendor chosen to monitor and manage step counts. Participants were also asked to voluntarily provide basic information (age, sex, job role, work location) and complete the Physical Activity Vital Sign (minutes/week and intensity of PA) at enrollment and 10 weeks. For 10 weeks, participants were sent a message through their employee ‘MyChart’ portal with a link to information on the benefits of PA, and a reminder of that week’s step-count challenge. Those meeting criteria for weekly challenges were included in gift card raffles. Participants were randomized 1:1 to receive the standard MyChart message +/- additional emails detailing their progress. Comparisons between groups included independent samples t-tests, Wilcoxon signed-rank tests, and chi-squared tests, with linear mixed effect modeling to assess predictors of step counts. Associations between variables were assessed using Cohen’s kappa.

Results:
3528 employees registered to participate (8% of all employees) although active users diminished over time (1225 at week 10). Average daily steps remained stable throughout (7319
+
4540 in week 1, 7229
+
5010 in week 10). Although there was no difference in any individual week, receipt of personalized feedback was associated with significantly higher average step counts throughout the 10-wk intervention as a whole (p=0.01). Age and an urban work location were positively associated with steps, while female sex and a clerical job role were negatively associated with steps counts (all p<0.005).

Conclusion:
Our findings provide important insight for the promotion of population health, and specifically, workplace interventions. They further suggest specific groups that may benefit from targeted efforts.
Abstract 4138948: Identifying atrial fibrillation symptom clusters and examining associations with major adverse cardiovascular events following catheter ablation
Authors: Reading Meghan , Scharp Danielle , Zhao Yihong , Hobensack Mollie , Van Bulck Liesbet , Volodarskiy Alexander , Slotwiner David
Published: November 2024

Introduction:
Atrial fibrillation (AF) is associated with a heavy burden of symptoms that frequently co-occur. Patterns of co-occurring symptoms and improvements after AF treatments are poorly understood. Disentangling AF symptoms can support better clinical management.

Objective:
This study aims to (1) identify co-occurring symptoms, or clusters, of patients undergoing catheter ablation for AF and (2) determine associations between symptom clusters and post-ablation AF-related major adverse cardiovascular events (MACE).

Methods:
We conducted a retrospective secondary analysis of electronic health record (EHR) data for adults who underwent catheter ablation for treatment of AF at one academic medical center from 2010-2020. We used a natural language processing algorithm developed by our team (F-score=0.81) to extract ten symptoms from clinical notes: anxiety, chest pain, dizziness, dyspnea, edema, fatigue, malaise, palpitations, syncope, and weakness. To conduct symptom clustering, we used an unsupervised machine learning approach, Ward’s hierarchical agglomerative clustering, to identify subgroups of patients representing different clusters. The composite AF-related MACE variable included AF-specific ED visit, AF-specific hospitalization, stroke, and/or death within one year post-ablation documented in EHRs. We used logistic regression models to examine associations between the six symptom clusters and the AF-related MACE outcome, adjusting for age, sex, and race.

Results:
The mean age of the sample (n=1,292) was 65.5 (standard deviation 12.6) years, 35% were female, and 58% were White. We identified six distinct clusters from notes (n=13,416), labeled using the most prevalent symptoms in each cluster: generally symptomatic, dyspnea and edema, chest pain, anxiety, asymptomatic, and fatigue and palpitations. One-third (n= 372; 29%) had an AF-related MACE within one year of ablation. The prevalence of symptom clusters within the sample and associations with MACE are shown in
Table 1
.

Conclusions:
AF patients’ pre-ablation symptoms vary widely and correlate with post-ablation MACE. It is possible symptom clusters signify latent biological differences with implications for the clinical care of AF.
Abstract 4138960: Survival Outcomes of Adults with Fontan Circulation Followed in an ACHD Center
Authors: Freddo Andrew , Eron Molly , Mondal Antara , Zavez Alexis , Denduluri Srinivas , Partington Sara , Ruckdeschel Emily , Tsao Allison , Vaikunth Sumeet , Kim Yuli
Published: November 2024

Introduction:
More patients with Fontan circulation are surviving into adulthood and transitioning to adult congenital heart disease (ACHD) care. There are limited long-term outcome data in these patients.

Research Questions:
We sought to describe a cohort of adults with Fontan circulation and determine patient characteristics associated with long-term survival.

Methods:
A retrospective review of adults with Fontan circulation followed in our ACHD clinic between 2009 and 2023 was performed. The outcome of interest was transplant-free survival. Survival analysis was performed to explore association between patient factors and time from Fontan completion to patient death or transplant. Patients without events were censored at last follow-up date.

Results:
In our cohort of 429 patients, median age at first ACHD visit was 24 (IQR 22-29) years with median follow-up time of 3.9 (IQR 0.6-6.4) years. The most common underlying anatomies were tricuspid atresia (26.5%) and hypoplastic left heart syndrome (25.4%). Fontan completion, most commonly lateral tunnel (59.1%), was performed at a median age of 29.7 months. Extracardiac comorbidities in our cohort included: cirrhosis (42.9%), cyanosis (25.9%), and protein losing enteropathy (PLE) (7.0%). Forty-one patients (9.6%) died, 17 (4.0%) had a heart-liver transplant, and 2 (0.5%) had a heart transplant. Transplant-free survival at 20, 30, and 40 years after Fontan completion was 99%, 87%, and 63%. In total, 10 patients died from end-stage heart failure, 8 from sudden cardiac arrest, and 5 from post-transplant complications (Figure). Morphologic right ventricle, cirrhosis, cyanosis, and PLE were associated with worse transplant-free survival (Table).

Conclusions:
Factors associated with decreased transplant-free survival in a cohort of adult patients with Fontan circulation were identified. These data highlight the importance of early identification and potential intervention for these comorbidities to improve long-term outcomes.
Abstract 4138981: Indication and electrical performance of conventional, resynchronisation and conduction system pacing in Transthyretin Amyloid Cardiomyopathy (ATTR-CM)
Authors: Dobner Stephan , Tawo Serlha , Wieser Fabian , Graeni Christoph , Haeberlin Andreas
Published: November 2024

Background:
Conduction system disease, atrial and ventricular arrhythmias may require pacemaker or ICD implantation in transthyretin amyloid cardiomyopathy (ATTR-CM). The optimal pacing mode in ATTR-CM patients remains unknown.

Objective:
To assess how availability of cardiac resynchronization and conduction system pacing influenced pacemaker indications and to compare early electrical performance of conventional, resynchronisation and conduction system pacing in ATTR-CM.

Methods and Results:
67 of 250 (26.8%) patients presenting with ATTR-CM between June 2019 and February 2023 received a pacemaker [HA1] and were included in this retrospective analysis. Pacemaker implantation occurred in 25 patients (37.3%) prior to, and in 42 (62.7%) after ATTR-CM diagnosis. Implantation of conventional single- (VVI) or dual-chamber (DDD) pacemakers was more common (n=17/25, 68%) in undiagnosed ATTR-CM, while physiological pacing systems (CRT/ CSP) were preferably implanted in patients (n=24/42; 57.1%) after diagnosis. Sick sinus syndrome (11/35; 31.4% vs. 6/32; 18.8%) and higher degree AV-block (20/35; 57.1% vs. 9/32; 28.1%) were more common indications for VVI/DDD compared to CRT/CSP pacemakers, with pursuit of a pace/ablate strategy (12/32; 37.5%) and heart failure (5/32; 15.6%) contributing significantly to implantation of CRT/CSP. QRS width was significantly lower with CSP [122ms (IQR: 120-139)], compared to CRT [155ms (IQR: 141-160); p=0.005] or VVI/DDD [160ms (IQR: 144-180)], with the latter resulting in a significant increase in QRS width compared to intrinsic QRS [from 138 (IQR: 123-150) (p<0.001)]. LV/LBBAP pacing capture thresholds (0.4ms pulse width) were significantly lower after CSP [0.75V (IQR: 0.5-1.2)] compared to CRT [1.3V (IQR: 1.0-1.6); p=0.049]. RA and RV lead performance were comparable between all pacing systems (p>0.05).

Conclusions:
Pacing indications are changing with earlier diagnosis of ATTR-CM. CSP may offer improved electrical performance and resynchronization, the effect of conduction system pacing on clinical outcomes should be further explored.
Abstract 4138984: Investigation of the effect of aortic valve replacement in severe aortic stenosis and transthyretin cardiac amyloidosis
Authors: Fujimoto Tomotaka , Zen Kan , Yamano Tetsuhiro , Matsubara Yuki , Iwaya Takuma , Takahara Motoyoshi , Yashige Masaki , Yamano Michiyo , Numata Satoshi , Nakamura Takeshi , Matoba Satoaki
Published: November 2024

Wild-type transthyretin amyloidosis (ATTR) is a potential one of the underlying causes of heart failure in the elderly, and in recent years, the complication rate with severe aortic stenosis (AS) has been reported to be higher than previously expected. We suspected cardiac amyloidosis (CA) in 142 of 824 patients referred for Severe AS between March 2020 and December 2023 and screened according to guidelines. Pathology was able to diagnose cardiac amyloidosis in 13 cases (1 immunoglobulin light chain, 11 ATTR, and 1 case of unknown type). Four cases were positive for technetium 99m pyrophosphate cardiac imaging and pathology could not be confirmed. Technetium 99m pyrophosphate cardiac imaging was negative in 125 cases. Of these, 115 patients (10 patients of ATTR-AS vs. 105 patients of Lone AS) who could be followed up after 6 months were compared. The median age of all patients was 85 years (interquartile range: 83 to 88) and 30.4% were male (60.0% vs. 27.6%; p=0.065). Pre-operative high-sensitivity troponin I values were higher in ATTR-AS group (58.2 [42.1 to 177.2] pg/mL vs. 20.2 [11.1-47.5] pg/mL; p=0.001), left ventricular ejection fraction tended to be lower (51.7 [41.7 to 58.8] % vs. 63.6 [54.3 to 69.3] %; p=0.015) and left ventricular mass index (LVMi) was significantly higher; no significant differences in AS severity were observed. Only one case of ATTR-AS was treated with surgical aortic valve replacement (AVR), while the other cases were treated with transcatheter AVR. Six months after AVR, there was no regression of LVMi and no statistically significant improvement in left ventricular diastolic and systolic performance in ATTR-AS group. Furthermore, New York Heart Association cardiac function classifications tended to have residual symptoms. The effect of therapeutic intervention on the aortic valve may be limited in ATTR-AS and is reported with a literature review.
Abstract 4139014: Building Nucleic Acid-Based Hirudins：Potent, Selective, and Reversible Protease Inhibitors
Authors: Yu Haixiang , Yan Amy , Pitoc George , Garber Susannah , Clancy Jeffrey , Sullenger Bruce
Published: November 2024

Background:
Unfractionated heparin (UFH), the main anticoagulant used in heart surgeries, is associated with adverse effects such as bleeding and heparin-induced thrombocytopenia. Anticoagulant aptamers targeting coagulation proteases have advantages such as low immunogenicity, low bleeding risk, and reversibility by complementary oligonucleotides. However, the potency of aptamers is often limited as they do not directly inhibit the catalytic sites on their targeted proteases. The natural anticoagulant hirudin achieves potent activity by inhibiting both thrombin’s exosite and active site. We hypothesize that hirudin-like protease inhibitors can be generated
de novo
by linking EXosite-binding aptamers with small molecule ACTive site inhibitors to create EXACT inhibitors that are much more potent than the small molecule inhibitors or aptamers alone.

Methods:
Protease inhibition by EXACT inhibitors were characterized by fluorogenic substrate cleavage assays. The anticoagulation activity of EXACT inhibitors was assessed in normal pooled plasma or whole blood using the standard clinical clotting assays: prothrombin time (PT), activated partial thromboplastin time (aPTT), and active clotting time (ACT). The clinical potential of the EXACT inhibitor was evaluated in an
ex vivo
Extracorporeal Membrane Oxygenation (ECMO) circuit that mimics the procoagulant environment in many cardiovascular surgical settings.

Results:
An EXACT inhibitor termed HD1-12dmA-DAB was synthesized by attaching the DNA aptamer HD1, that binds to thrombin exosite I, through a poly-adenosine linker to the thrombin active site inhibitor dabigatran (DAB). The EXACT inhibitor showed stronger thrombin inhibition (IC
50
= 0.2 nM) than DAB (IC
50
= 80 nM) or HD1 (IC
50
> 1 µM) alone. HD1-12dmA-DAB (2 µM) also achieved equal or higher anticoagulant activity than UFH (5U/mL) in all clotting assays and showed anticoagulation efficacy rivaling UFH in the
ex vivo
ECMO circuit with minimal clot observed over 120 min. Notably, the EXACT inhibitor’s effect can be rapidly reversed by an antidote oligo. We also used the same strategy to develop a potent EXACT inhibitor against factor Xa.

Conclusions:
EXACT inhibitors demonstrate extraordinary anticoagulation activity as potential rapid onset anticoagulants to support cardiovascular procedures. Using this generalizable strategy, selective, potent, and rapidly reversible EXACT inhibitors can be created against many enzymes for numerous therapeutic applications.
Abstract 4139017: Carotid Plaque Score by Ultrasound and its Prediction of Carotid Plaque Burden by MRI and Cardiovascular Events
Authors: Chew Christopher , Dardari Zeina , Razavi Alexander , Nasir Khurram , Matsushita Kunihiro , Santilli Francesca , Lavalle Augusto , Albrecht Gerhard , Nambi Vijay , Johri Amer , Wasserman Bruce , Dzaye Omar , Blaha Michael
Published: November 2024

Introduction:
Imaging modalities are crucial for enhancing atherosclerotic cardiovascular disease (ASCVD) risk assessment. With total plaque burden recently recognized as perhaps a superior predictor for ASCVD, there has been a shift toward measuring carotid plaque burden rather than only stenosis on carotid artery ultrasound (CA US). We aimed to assess the association between carotid plaque burden detected by CA US and carotid artery magnetic resonance imaging (CA MRI) and their predictions for ASCVD events.

Methods:
Participants free of known ASCVD who underwent CA US at Visit 4 and/or CA MRI within the ARIC cohort were included. A composite carotid plaque score (CPS, ranging 0-6) was derived from CA US based on plaque presence in the left and right common, bifurcation, and internal carotid arteries. CA MRI measures included total wall volume, maximum wall thickness, maximum stenosis, and lipid core area. Adjusted linear regression was used to identify prospective associations between the CPS and natural log-transformed CA MRI measures. Proportional hazard Cox analyses were used to determine the associations between the CPS/CA MRI measures and ASCVD events.

Results:
In this analysis, 6,149 participants had CA US data available, 1,456 participants had CA MRI data available, and 877 had both. The mean time between CA US and CA MRI was 9 years. The mean age at CA US was 63 years old, 58% were women, and 1,568 participants had an ASCVD event with a median follow up time of 20 years. The presence of carotid plaque on CA US was significantly associated with composite ASCVD events and stroke only. The CPS had stepwise higher HRs across increasing intervals
(Table 1a)
and was significantly associated with natural log-transformed CA MRI measures after adjustment
(Table 1b)
. C-statistics for models predicting composite ASCVD events and stroke were similar for both CA US and CA MRI.

Conclusion:
The CPS had an independent association with both ASCVD events and stroke alone. It had a similar significant association with key CA MRI measures, suggesting that the CPS may predict future carotid plaque on CA MRI. Thus, the CPS may be a simpler yet effective method to quantify subclinical carotid plaque and improve ASCVD risk assessment.
Abstract 4139032: Torsemide versus furosemide for hospitalization in patients with heart failure: a meta-analysis and trial sequential analysis
Authors: Barbosa Lucas , Araujo Beatriz , Queiroz Ivo , Almiron Giulia
Published: November 2024

Background:
Furosemide is the most commonly used loop diuretic in patients with heart failure (HF). However, recent studies suggest that torsemide might be a better option, potentially reducing hospitalization rates. This meta-analysis aimed to compare the effectiveness of torsemide versus furosemide in patients with HF.

Methods:
We systematically searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) comparing torsemide versus furosemide in HF patients. We pooled risk ratios (RR) for binary outcomes, and mean differences (MD) for continuous outcomes with 95% confidence intervals (CI) with a random-effects model. We performed a trial sequential analysis (TSA) to assess the random risk of HF-related hospitalizations. We used R version 4.3.2 and TSA version 0.9.5.10 for statistical analyses.

Results:
Our meta-analysis included 9 RCTs comprising 4077 patients, of whom 2014 (49.4%) were randomized to torsemide. The mean age was 65.9 years old. Torsemide significant reduced the HF-related hospitalizations (RR 0.61; 95% CI: 0.45 to 0.83; p<0.05; Figure A), cardiovascular hospitalization (RR 0.73; 95% CI: 0.61 to 0.89; p<0.05; Figure B), and all-cause hospitalization (RR 0.95; 95% CI: 0.90 to 0.99; p<0.05; Figure C). However, there were no significant differences in all-cause mortality (RR 0.98; 95% CI: 0.88 to 1.11; Figure D) between groups. Additionally, for the primary endpoint, TSA suggested a low risk of type 1 error; therefore, this result may be conclusive (Figure E).

Conclusion:
In patients with heart failure, torsemide significantly reduced the incidence of hospitalizations. However, it appears not to have significant benefits in mortality rates.
Abstract 4139035: Health Literacy in Men and in Women With Type 2 Diabetes Undergoing Coronary Angiography
Authors: Neyer Magdalena , Vogel Johannes , Elsner Pascal , Plattner Thomas , Vonbank Alexander , Mader Arthur , Larcher Barbara , Leiherer Andreas , Muendlein Axel , Frick Matthias , Drexel Heinz , Saely Christoph H
Published: November 2024

Health literacy reflects the ability to make appropriate health decisions and affects health outcomes. It therefore is an important parameter in patient care and for health care providers. Health literacy in patients undergoing coronary angiography, the standard procedure for the definite evaluation of coronary artery disease (CAD) is unclear and is addressed in the present study.

We recruited 515 consecutive patients (383 men and 132 women) undergoing coronary angiography for the evaluation of established or suspected stable CAD in a tertiary care setting in central Europe. Health literacy was measured using the validated HLS-EU-Q16 questionnaire.

A response rate of 80.4% was achieved. Overall, 177 patients (i.e. 34.3% of the cohort) had type 2 diabetes (T2DM); the prevalence of T2DM was 36.8% in men and in 27.3% in women (p=0.047). Comparing T2DM patients to those who did not have diabetes, overall median health literacy scores (HLS) were 13 [IQR=11-15] vs. 13 [IQR=10-15] among men (p=0.424) and 12 [IQR=10-15] vs. 13 [IQR=10.25-15] among women (p=0.517). Prevalence rates of adequate (HLS 13-16), problematic (HLS 9-12) and inadequate (HLS 0-8) health literacy did not differ significantly between patients with T2DM vs. subjects without T2DM (53.0% vs. 55.4%, 34.8% vs. 29.9% and 12.2% vs. 14.7% among men and 37.5% vs. 55.6%, 45.8% vs. 31.9% and 16.7% vs. 12.5% among women, respectively.

We conclude that among patients undergoing coronary angiography for the evaluation of established or suspected stable CAD, health literacy regardless of sex is suboptimal both in patients with T2DM and in non-diabetic subjects.
Abstract 4139038: Ibrutinib Increases Phosphorylation of the Src-Erk1/2 Signaling Pathway in Human Atrial-Specific Cardiomyocytes Derived from Induced Pluripotent Stem Cells
Authors: Fleming Matthew , O'Neill Matthew , Yang Tao , Solus Joseph , Kroncke Brett , Knollmann Bjorn , Moslehi Javid , Roden Dan
Published: November 2024

Background:
The Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib has revolutionized treatment for B-cell malignancies but increases the incidence of atrial fibrillation (AF) compared with conventional chemotherapy. Reports indicate that ibrutinib-mediated AF does not result from inhibition of BTK, but from off-target inhibition of a different kinase, C-terminal Src kinase (CSK). The signaling pathway by which CSK inhibition results in AF is unknown and may represent a novel molecular mechanism for AF.

Objective:
To identify kinase pathways that promote atrial fibrillation downstream from CSK.

Methods:
Studies were performed in human atrial-specific cardiomyocytes (hiPSC-aCMs) derived from population control induced pluripotent stem cells. Extracellular field potentials (EFPs) with the Nanion CardioExcyte 96 system demonstrated marked increased spontaneous beat-to-beat variability, an in vitro correlate of arrhythmogenic behavior, with exposure to ibrutinib but not to second-generation BTK inhibitors, which are less associated with AF (Figure 1A). Human phospho-kinase arrays determined the relative phosphorylation of 37 kinases in hiPSC-aCMs treated with ibrutinib or vehicle.

Results:
Treatment with ibrutinib increased phosphorylation of multiple kinases (Src, Erk1/2, CREB) in the Src-Erk1/2 pathway (Figure 2); the biggest increase was with Erk1/2 phosphorylation (3-fold). Pre-treatment of hiPSC-aCMs with the Erk1/2 inhibitors ulixertinib and SCH772984 inhibited the EFP arrhythmogenic signal seen with ibrutinib (Figure 1B).

Conclusion:
In hiPSC-aCMs, inhibition of CSK by ibrutinib results in increased arrhythmogenic behavior through Erk1/2-dependent phosphorylation. The downstream mechanisms by which this occurs remain unknown and represent novel potential target(s) for AF therapeutics.
Abstract 4139043: Artificial intelligence-enabled detection and phenotyping of left ventricular hypertrophy on real-world point-of-care cardiac ultrasonography and its implications for patient outcomes
Authors: Oikonomou Evangelos , Holste Gregory , Coppi Andreas , Baloescu Cristiana , McNamara Robert , Khera Rohan
Published: November 2024

Introduction:
Point-of-care ultrasonography (POCUS) is routinely performed across emergency departments (EDs), but interpretation is generally restricted to acute pathology. We sought to evaluate the outcomes of individuals who had undergone an ED POCUS, but were never diagnosed with cardiomyopathy, using artificial intelligence (AI)-defined signatures of left ventricular hypertrophy (LVH) and key sub-phenotypes (hypertrophic cardiomyopathy [HCM], transthyretin amyloid cardiomyopathy [ATTR-CM], and aortic stenosis [AS]) on POCUS.

Methods:
First, using 261,756 videos from 9,667 standard transthoracic echocardiograms (TTEs) across a large, diverse health system, we trained a view quality-adapted, video-based deep learning model to detect a) LVH, representing the mean of a multi-label classifier for i) moderate or greater nominal severity as reported by the echocardiographer; ii) left ventricular posterior wall thickness [LVPWd] of ≥1.3 cm, and/or iii) interventricular septum thickness [IVSd] of ≥1.3 cm, and b) known cardiomyopathy defined by non-mutually exclusive labels of i) ATTR-CM, ii) HCM, and/or iii) AS (
Fig. 1A
). We deployed these tools among adult patients without known cardiomyopathy who underwent clinical POCUS across EDs (2013-2023) linked to in-hospital and out-of-hospital death data. We explored the association between distinct label output probabilities and all-cause mortality in age- and sex-adjusted Cox regression models (
Fig. 1B
).

Results:
Among 24,448 individuals (median age 58, [IQR 40-73] years; 13,478 [55.1%] women) followed over 2.2 [IQR: 1.1-5.8] years, higher AI-POCUS probabilities for LVH were associated with worse long-term prognosis, with a 29% higher mortality risk in the highest vs lowest AI-defined quintile (adj. HR 1.29 [95%CI: 1.13, 1.46]) (
Fig. 2A
). When stratifying based on the probability of distinct phenotypes, an ATTR-CM-like phenotype in the highest (vs lowest) quintile conferred a 39% higher adjusted risk of death (adj. HR 1.39 [95%CI: 1.22, 1.59]) (
Fig. 2B
). Similarly, there was a 14% (adj. HR 1.14 [95%CI: 1.01, 1.30]) and 15% (adj. HR 1.15 [95%CI: 1.02-1.29]) higher risk of death in the highest (vs lowest) AS (
Fig. 2C
) and HCM (
Fig. 2D
) phenotypic quintiles, respectively.

Conclusions:
AI-enabled automated identification and phenotyping of LVH is feasible on routine POCUS studies and identifies individuals who are at risk of premature mortality, potentially due to undiagnosed cardiomyopathy.
Abstract 4139107: Association of Patient Healthcare Information Exchange Systems at US Hospitals with 30-day Excess Days in Acute Care after Heart Failure Hospitalization
Authors: Pedroso Camargos Aline , Lin Zhenqiu , Ross Joseph , Khera Rohan
Published: November 2024

Background:
Given its chronicity and high hospitalization burden, heart failure (HF) requires close coordinated care. Health Information Exchange (HIE) systems can improve care by enabling seamless information sharing between healthcare providers and patients. We evaluated whether hospitals that have invested in more comprehensive HIE access for patients have better risk-standardized post-discharge outcomes after HF hospitalization.

Methods:
We defined a range of contemporary HIE services at all US acute care hospitals using the American Hospital Association (AHA) Information Technology (IT) Annual Survey (2022). HIE services included mobile access to health records, the ability to import, export, and update health records online, and the option to share patient-generated data with the health system, representing health measurements and data generated from smart devices (
A
). We identified each hospital’s corresponding 30-day excess days in acute care (EDAC) for HF – a risk-standardized metric of all acute care needs in the post-hospitalization period from the Centers for Medicare&Medicaid Services Quality Report (2019-2022) and examined the association between HIE services and 30-day EDAC for HF using multivariable linear regression.

Results:
There were 2,581 US hospitals (22% rural, 9% teaching, with a median bedsize of 162 [IQR 76, 307]) in the AHA-IT survey, with a median EDAC of 5.9 (IQR -8.6, 20.9) days for HF. The vast majority (99%) of hospitals had online health record portals, but access to specific HIE services varied widely across hospitals (
B
): 84% offered access via mobile application, 86% allowed data import, 55% data export to other health systems, and 77% online data updates, with fewer than half (47%) allowing patients to share patient-generated health data. After accounting for differences in hospital characteristics, only hospitals with HIE configured to enable patients to share their personal health data directly with the health system had significantly lower risk-standardized 30-day EDAC for HF (-3.9, 95% CI -1.04, -3.48) (
C
).

Conclusions:
Hospitals with HIE services that include the sharing of patient-generated data have significantly better risk-standardized post-hospitalization outcomes for HF. There is a need to evaluate the role of broader access to bidirectional data sharing as a strategy to enhance care and outcomes at hospitals treating patients with ongoing post-discharge needs.
Abstract 4139207: Supraselective Administration of Very Low-dose Intracoronary Epinephrine as a Rescue and First-line Drug for the Management of No-reflow in Conjunction With the IIB-IIIA Inhibitor Tirofiban.
Authors: Correa Bastidas Roberto , Correa Soto Roberto
Published: November 2024

Background:
Occurring in 0.6% to 10% of percutaneous coronary interventions (PCI), no-reflow is a complication associated with poor outcomes like myocardial infarction extension and death. The mechanism behind no-reflow is complex and likely multifactorial, and several drugs have been described for its management including intracoronary epinephrine (ICE) at doses ranging from 50 to 400 µg.

Hypothesis:
We hypothesize that supraselective administration of ICE at very low doses could be effective in the successful management of no-reflow.

Methods:
This single-center case series from Bucaramanga, Colombia (August 2021-October 2023) reports on 9 patients with/without ST-segment elevation myocardial infarction who underwent PCI and developed no-reflow. As first-line therapy for no-reflow management, supraselective administration of 5 to 50 µg of ICE was performed through an ad hoc fenestrated angioplasty balloon with a two-way drug perfusion technique (proximal to distal, and distal to proximal) at an approximate rate of 2 µg/min. All patients received a 1000 µg intracoronary bolus of Tirofiban during the procedure, and an IV infusion of 0.15 µg/kg/min was continued up to 24 hours postangioplasty.

Results:
The mean age of patients was 72.7±10.6 years, and 8 out of 9 patients were male. The mean LVEF was 34±11.3% before PCI. Patients received varying doses of ICE (5, 10, 20, 40 and 50 µg), 7 received it as the first-line treatment, while 2 received it as a second-line option after 360 µg of intracoronary adenosine failed to improve blood flow. TIMI 2 flow (4 patients) and TIMI 3 flow (5 patients) were achieved with no consistent association between higher ICE doses and achieving TIMI 3 flow. All 9 patients were discharged alive from the Cath Lab. However, one patient with LVEF 20% died of pulmonary edema 7 hours postangioplasty. The mean heart rate before and after the procedure was 78±20.8 bpm and 84±18.3 bpm respectively. No severe cardiac arrhythmias were observed. Transient inotropic support with a norepinephrine infusion was needed by 2 patients.

Conclusion:
The supraselective administration of ICE at very low doses (5-50 µg) resolved no-reflow in 100% of patients with acute coronary syndrome. We propose the use of this drug at very low doses as a first-line therapy for the management of coronary no-reflow, as well as the development of future randomized control trials to evaluate its effectiveness, and compare it to current therapies, in a larger population.
Abstract 4139216: The tolerability, safety, pharmacokinetics, and pharmacodynamics of TX000045, a long-acting Fc-relaxin fusion protein after single doses in healthy volunteers
Authors: Ruddy Marcella , West Mary , Milton Mark , Muslin Anthony
Published: November 2024

Introduction:
TX000045 (TX45) is a long-acting Fc-relaxin fusion protein with vasodilatory, anti-fibrotic and anti-inflammatory activity due to selective agonism of the G protein-coupled relaxin family peptide receptor 1 (RXFP1). It is being developed for Group 2 pulmonary hypertension associated with heart failure with preserved ejection fraction (HFpEF). This first-in-human study evaluated the safety/tolerability, pharmacokinetic and pharmacodynamic profile of TX45 in healthy volunteers after single doses.

Methods:
This phase 1a, randomized, double-blind, placebo-controlled single ascending dose study was performed in seven cohorts of healthy volunteers. Six cohorts consisted of eight patients receiving intravenously (IV) or subcutaneously (SC) one of several doses of TX45 (n=6 on treatment) or placebo (n=2), including 0.3 mg/kg IV, 1 mg/kg IV, 3 mg/kg IV, 150 mg SC (x2 cohorts), and 300 mg SC. One cohort consisted of seven patients receiving 600 mg SC TX45 (n=5 patients) or placebo (n=2 patients). The goals of the study were to assess the tolerability and safety, immunogenicity, pharmacokinetic (PK) and pharmacodynamic (PD = renal plasma flow, RPF) properties of TX45 in healthy volunteers after single doses. RPF was determined by analysis of steady-state para-aminohippurate (PAH) blood levels in response to a PAH IV infusion.

Results:
55 healthy volunteers were randomized. TX45 was well tolerated. Most adverse events were mild to moderate in intensity. The most common treatment emergent adverse event was transient orthostatic tachycardia, not associated with hypotension. TX45 demonstrated linear pharmacokinetics across the dose range with a terminal half-life estimated to be 13-23 days. Treatment with TX45, across dose levels, increased renal plasma flow by 16-42%, consistent with known relaxin effects. Leveraging repeated measures of renal plasma flow post dose, TX45 demonstrated prolonged maintenance of a pharmacodynamic effect. There was no evidence of immune mediated clearance of TX45.

Conclusions:
TX45 was generally well tolerated with a safety, pharmacokinetic and pharmacodynamic profile to support further clinical development. Its maximum effect on RPF is similar to previously described effects of native relaxin. Its half-life will support a prolonged dosing interval. These findings support further evaluation of TX45 in patients with Group 2 pulmonary hypertension associated with HFpEF.
Abstract 4139235: Colorectal Cancer Incidence in Heart Transplant Recipients: A Competing Risks Analysis
Authors: Tajerian Amin , Abboud Alan , Charles Sharon , Clores Michael , Goldschmidt Marc , Aroniadis Olga , Kalogeropoulos Andreas
Published: November 2024

Background:
Colorectal cancer (CRC) risk is elevated in solid organ transplant recipients. However, data on CRC risk in heart transplant (HT) patients are limited. Also, screening recommendations for CRC in the HT population, especially patients under age 45, are lacking. Previous studies have been constrained by single-center designs, outdated cohorts, and lack of competing mortality analysis.

Objectives:
We aimed to assess competing-risk incidence of post-HT CRC, with focus on the effect of age, to inform CRC screening recommendations.

Methods:
We identified patients ≥18 years old at the time of HT in the TriNetX Research Network, which encompasses healthcare records from over 80 systems in the US, using CPT codes for HT (33945) and combined lung-HT (33935). CRC was identified from ICD-10 CM codes (C18, C19&C20). Because mortality is significantly higher than CRC risk in this population, we used the Fine and Gray competing-risks framework to estimate CRC incidence for the entire cohort and subgroups of interest.

Results:
We identified 4791 patients with HT or lung-HT between 1996 and 2024. After excluding 275 patients because of missing (N=266) or too short (N=9) follow-up, 4516 patients were included (
Table 1
). After a median follow up of 3.6 years (25
th
– 75
th
percentile, 1.4 – 6.7), 48 patients developed CRC. The median time from HT to CRC was 4.5 years (0.7 – 8.0) and the median age at CRC was 65 (55 – 71). The cumulative incidence, adjusting for competing mortality, was 0.68% (95%CI: 0.45%, 1.0%) at 5 years and 1.7% (95%CI: 1.2%, 2.4%) at 10 years (
Figure 1
), corresponding to an incidence rate of 170 cases per 100,000 patient-years, and did not differ between men and women (180 vs. 120; P=0.7). In comparison, all-cause mortality was 20% at 5 years and 38% at 10 years. Age at HT was not significantly associated with CRC risk (P=0.22); patients age <45 at HT experienced similar risk as patients ≥45 (
Table 2
). In comparison, the age-adjusted CRC rate in the US population for years 2016-2020 was 42 and 32 cases per 100,000 patient-years in men and women, respectively. Year of HT was not associated with CRC risk (P=0.69).

Conclusion:
In this cohort of HT recipients, the absolute CRC risk was lower compared to previous reports that did not account for the competing risk of death. However, rates of CRC were much higher compared to the general population and did not differ by age at HT, suggesting that all HT patients should be screened for CRC regardless of age.