bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4143175: Real-world Long-term Effectiveness of Mavacamten in Patients with Symptomatic Obstructive Hypertrophic Cardiomyopathy: a Multicenter Observational Study (MARVEL-HCM)
Authors: Abraham Theodore , Alsidawi Said , Martinez Matthew , Wheeler Matthew , Roehl Kaitlin , Patel Ruchi , Soutar Marybeth , Herry Morgane , Wang Manchen Annie , Kim Mi-Ok , Schuler Patricia , Dubey Anand
Published: November 2024

Background:
Mavacamten was approved by the US Food and Drug Administration (FDA) in April 2022 for the treatment of adults with New York Heart Association (NYHA) class II-III symptomatic obstructive hypertrophic cardiomyopathy (HCM). Few studies have reported on the long-term real-world effectiveness and safety of mavacamten. We evaluated clinical outcomes in patients on mavacamten in multiple health centers across the United States.

Research Questions:
This study assessed the real-world effectiveness and safety of mavacamten in patients with symptomatic obstructive HCM.

Methods:
In this multi-center observational study, we evaluated patient characteristics at baseline, NYHA class, left ventricular outflow tract gradients (LVOTg) at rest and Valsalva, and left ventricular ejection fraction (LVEF) in patients with symptomatic obstructive HCM treated with mavacamten for up to 72 weeks.

Results:
Mavacamten was initiated in 172 patients across 4 US centers (UCSF, Mayo Arizona, Stanford, and Atlantic Health System/Morristown Medical Center). Baseline characteristics included: 56% female, mean age 64 (standard deviation ±13) years, 47% NYHA class III, mean resting LVOTg of 47 mmHg and mean Valsalva LVOTg of 89 mmHg, and 23% non-White. Comorbidities included hypertension (56%) and atrial fibrillation (25%) at baseline (Table). Patients experienced a notable early response to mavacamten in resting and Valsalva gradients by week 4, which was sustained through week 72 (Figure A). No patients were NYHA class III at week 72, compared to 47% at baseline (Figure B). Mean LVEF did not change substantially between baseline and week 72. No patients experienced an LVEF of <40% and 2% experienced an LVEF of <50%.

Conclusions:
This is the largest observational study to date demonstrating the effectiveness and safety of mavacamten with substantial sustained reductions in resting and Valsalva LVOTg, and progressive improvements in NYHA class without considerable changes in mean LVEF up to 72 weeks.
Abstract 4143192: Co-incidence of postoperative delirium and atrial fibrillation is associated with elevated risk of one-year mortality after cardiac surgery
Authors: Abbas Mostafa , SHARMA ROHIT , Morland Thomas , Shuhaiber Jeffrey , Kirchner H Lester , LeMaire Scott , El-Manzalawy Yasser
Published: November 2024

Background:
Delirium and atrial fibrillation (AF) are two common complications after cardiac surgery. Each of them has been associated with several other adverse outcomes including mortality and prolonged hospital stay. We sought to determine the frequency of the co-incidence of postoperative delirium (POD) and postoperative atrial fibrillation (POAF) and its association with risk of one-year mortality following cardiac surgery compared to POD or POAF alone.

Methods:
We established a retrospective observational cohort of adult patients who underwent cardiac surgery within our healthcare system between 2014 and 2022. POD was defined as a postoperative positive CAM-ICU test in a patient with a Richmond Agitation-Sedation Scale (RASS) >= -3. POAF was defined as a documented AF event within 30 days after surgery. Patients were stratified into four distinct groups: Co-incidence of POD and POAF, POD only, POAF only, and None (i.e., neither complication).

Results:
Among 6136 patients, there were 256 (4.2%) patients experienced both POD and POAF, 221 (3.6%) had POD only, 2127 (34.7%) had POAF only, and 3532 (57.6%) had neither complication. The overall one-year mortality rate was 5.8%, with mortality rates of 21.9% for the co-occurrence group, 14.0% for the POD only group, 6.8% for the POAF only group, and 3.5% for the group with neither complication. The differences in one-year survival among the four groups are shown in
Figure 1
. Multivariable logistic regression analysis identified the top predictors for one-year mortality as co-incidence of POD and POAF (adjusted odds ratio (OR)=3.98, 95% CI=2.69-5.85, p<0.001), POD only (OR=2.95, 95% CI=1.84-4.61, p<0.001), higher Charlson comorbidity index (OR=2.18, 95% CI=1.00-4.46, p=0.040), longer surgery duration per hour (OR=1.62, 95% CI=1.46-1.79, p<0.001), and POAF only (OR=1.50, 95% CI=1.15-1.97, p=0.003).

Conclusions:
More than half of the cardiac surgery patients with POD also developed POAF. The co-incidence of POD and POAF was associated with elevated risk of one-year mortality compared to either complication alone. Further research to explore the underlying mechanisms connecting POD and POAF and to identify risk factors specific to their co-incidence is warranted.
Abstract 4143199: The Multi-omic, Multi-tissue Response to Acute Endurance and Resistance Exercise: Results from the Molecular Transducers of Physical Activity Consortium
Authors: Katz Daniel , Jin Christopher , Smith Gregory , Clark Natalie , Iyer Gayatri , Keshishian Hasmik , Hart Patrick , Sanford James , Zhang Zidong , Ge Yongchao , Robbins Jeremy , Barber Jacob , Montalvo Samuel , Jimenez-Morales David , Lindholm Malene , Zhen Jimmy , Jaeger Byron , Sparks Lauren , Sagendorf Tyler , Many Gina , Vetr Nikolai , Raja Archana , Amar David , Hsu Fang-Chi , Miller Michael , Xia Ashley , Fleg Jerome , Tracy Russell , Gerszten Robert , Adkins Joshua , Walsh Martin , Sealfon Stuart , Goodpaster Bret , Trappe Scott , Burant Charles , Carr Steven , Smith Kevin , Snyder Michael , Montgomery Stephen , Ashley Euan , Wheeler Matthew , . MoTrPAC Study Group
Published: November 2024

Introduction:
Exercise is critical to cardiovascular health. However, the underlying molecular mechanisms are not well described. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) seeks to create a detailed molecular map of the response to exercise. Described here is the first human cohort of MoTrPAC, enrolled prior to the COVID-19 shutdown (N=175).

Methods:
Healthy, sedentary adults were randomized to an 8-exercise circuit of resistance exercise (RE, N=73), a 40 minute submaximal endurance exercise bout (EE, N=65), or to non-exercising control (N=37). Blood, muscle, and adipose tissue were sampled at 4-7 time points relative to exercise, depending on tissue/modality. Samples were deep phenotyped across multiple omic domains including chromatin accessibility, transcriptomics, proteomics, phosphoproteomics, and metabolomics.

Results:
The cohort was 72% female, with a mean±sd age of 41±15 years and BMI of 27.1±4.0 kg/m2. Exercise affected over 34,000 molecular features in ≥1 tissue/time point including a high proportion of transcriptomic and phosphoproteomic features (Figure A). Molecular signatures were compared between EE and RE: enrichment analysis of muscle phosphoproteomics showed a greater activation of MAP kinases in RE compared to EE at all time points. To identify plausible exerkines (secreted molecules signaling an acute exercise bout), differentially abundant features in any sampled tissue cells were compared to temporally-matched cognate protein levels in plasma, yielding 110 features. A known exerkine, CX3CL1 (fractalkine) was identified, in addition to novel candidates, such as cellular communication network factor 1 (CCN1), a secreted extracellular matrix protein linked to plasma triglyceride levels, which showed increased abundance early post exercise (Figure B). Network analysis across tissues and omes identified novel transcription factor “hubs” as candidate master regulators of exercise response.

Conclusions:
These first MoTrPAC data represent an unparalleled multi-tissue, multi-omic, multi-time point, multi-modality map of acute exercise, enhancing our understanding of the molecular transducers that may link exercise and cardiovascular health.
Abstract 4143291: Macrophage Drp1 Sulfenylation drives neovascularization and regeneration of ischemic muscle via promoting reparative polarization and metabolic reprograming
Authors: Yadav Shikha , Nagarkoti Sheela , Varadarajan Sudhahar , Das Archita , McMenamin Malgorzata , Kelley Stephanie , Fukai Tohru , Ushio-Fukai Masuko
Published: November 2024

Background:
Reactive oxygen species (ROS) function as signaling molecules to regulate reparative macrophage polarization essential for ischemia-induced neovascularization and regeneration of skeletal muscle in peripheral arterial disease (PAD). Mitochondrial fission protein Drp1 GTPase is involved in pro- and anti-inflammatory macrophage phenotype and metabolism in a context-dependent manner. However, mechanistic link between macrophage Drp1 and ROS-dependent reparative angiogenesis and muscle regeneration during ischemia is entirely unknown.

Methods and results:
Using a mouse Hindlimb ischemia (HLI) model, a preclinical model of PAD, here we show that macrophage-specific Drp1 knockout (KO) mice exhibited significant reduction of blood flow recovery, angiogenesis (CD31+ capillary) and muscle regeneration following HLI. Flow cytometry analysis revealed that these responses were associated with an initial increase in Lys6G+ neutrophils (4-fold), followed by reduction in anti-inflammatory F4/80+CD206+ M2 macrophage (2-fold) in ischemic muscle of Drp1 KO mice at days 3 and 7 post HLI. Mechanistically, Drp1-CysOH formation (sulfenylation), but not Drp1 phosphorylation, was increased in bone marrow (BM) and ischemic muscles after HLI, which was markedly reduced in CRISPR/Cas9-generated “redox-dead” Drp1-C631A (C/A) knock-in mutant (Drp1-C/A) mice. Functionally, BM chimera mice in which BM in wild type (WT) mice is replaced with Drp1-C/A mutant showed impaired limb perfusion recovery (30%), angiogenesis (45%) and muscle regeneration after HLI. In vitro PAD model showed that macrophage exposed to hypoxia serum starvation (HSS) had increased ROS production and Drp1-CysOH formation without Drp1 phosphorylation at 1 h after HSS stimulation. Macrophage isolated from Drp1 KO or Drp1-C/A mice under HSS exhibited inhibition of Drp1-CysOH formation, while increased glycolysis (ECAR, 50%), pro-inflammatory M1-genes and decreased M2-genes (40%).

Conclusion:
Cysteine oxidation of Drp1 in macrophage promotes revascularization and regeneration of ischemic muscle by driving reparative metabolic reprogramming and macrophage polarization. This process represents a novel therapeutic target for treatment of PAD.
Abstract 4143300: Atrial Function Improves Stroke Prediction in Patients with Atrial Fibrillation
Authors: Kassar Ahmad , Chamoun Nadia , Chahine Yaacoub , Akoum Nazem
Published: November 2024

Background:
Stroke contributes to significant morbidity and mortality in atrial fibrillation (AF). Clinical risk scores lack predictive accuracy and mechanistic links to thrombo-embolization.

Hypothesis
Adding MRI-derived parameters to stroke risk calculators improves their predictive accuracy.

Aims
Demonstrate an association between left atrial emptying fraction (LAEF), long axis strain (LAS) and stroke in AF patients.

Incorporating the above-mentioned LARF and LAS into the CHA
2
DVASc score improves its predictive accuracy.

Methods:
AF patients undergoing cardiac MRI were identified from the University of Washington Cardiac Arrhythmia Data Repository (CADRe). Pts with prior AF ablation were excluded from the study. LAEF and LAS were quantified using a semi-automated contouring of the LA wall was done through image processing software (CVI42®) (Panel A).

Results:
417 pts (average age 66±13years; 64% males) were included. The average CHA
2
DVASc (stroke component removed) score was 2.1±1.4. LAEF was 46.18%±11.64%, and LA LAS was 24.28%±13.45%. Univariate analysis revealed a significant association between stroke/TIA and LAEF (OR= 0.962, p= 0.024); but not with LAS (OR=0.962, p=0.091) or CHA
2
DVASc (OR=1.084; p=0.553). LAEF remained significantly associated with stroke in multivariate analysis, adjusting for age, gender, congestive heart failure, hypertension, coronary artery disease, and diabetes, (OR= 0.963, p= 0.042). Three other models including composite CHA
2
DVASc with and without LAEF with their respective ROC curves and AUC are shown in Panel B. Adding LAEF improved the AUC of CHA
2
DVASc (AUC 0.564 vs 0.653; p=0.048) or its components (AUC 0.539 vs 0.632; p=0.043). Using a cut-off LAEF of 46.53% (AUC: 0.71 CI: 0.61,0.81; Sensitivity: 68%; Specificity: 74%) resulted in the reclassification of 47(11.3%) pts to a higher risk category and none (0%) to lower risk (Panel C).

Conclusion:
Left atrial emptying fraction is independently associated with stroke or TIA, and improves the predictive accuracy of clinical risk scores in AF pts.
Abstract 4143303: Association of Preeclampsia with Long-Term Coronary Microvascular Dysfunction Utilizing Cardiac Stress Magnetic Resonance Imaging
Authors: Roy Rukmini , Wang Haonan , Huang Sherry , Minga Iva , Wang Shuo , O'Hara Meaghan , Tang Maxine , Slivnick Jeremy , Polonsky Tamar , Rana Sarosh , Lang Roberto , Patel Amit , Shahul Sajid , Patel Hena
Published: November 2024

Introduction:
Preeclampsia is a hypertensive disorder of pregnancy associated with cardiovascular disease. Systemic peripartum microvascular alternations have been implicated in pregnancies complicated by preeclampsia. Whether coronary microvascular dysfunction is a potential mediator of preeclampsia-associated cardiovascular risk is unknown. We aimed to determine whether individuals with a history of preeclampsia have coronary microvascular dysfunction measured by cardiac magnetic resonance imaging (CMR) at least 5 years postpartum.

Methods:
Women with singleton pregnancies complicated by preeclampsia and a comparator group with uncomplicated, normotensive deliveries were identified and prospectively enrolled to undergo regadenoson stress perfusion CMR (1.5T Signa Artist GE HealthCare) at least 5 years postpartum. Using the dual sequence technique, fully quantitative perfusion values were determined using Fermi deconvolution. Myocardial perfusion reserve (MPR) was calculated as the ratio of stress to rest myocardial blood flow (MBF).

Results:
Twenty-three subjects (41.0 ± 6 years, 12.7 ± 5 years post-partum) were included. Women with a history of preeclampsia (n=11) were compared to a control group of women with prior normotensive pregnancy (n=12) (
Figure 1A
). Obesity and diabetes were more common with preeclampsia, but there was no significant difference in the presence of hypertension between the groups (Table 1A). There was no difference in stress MBF. However, preeclampsia was associated with higher rest MBF (1.47 ± 0.54 mL/g/min vs. 1.19 ± 0.29 mL/g/min; p=0.07) and MPR (1.96 ± 0.46 vs 2.66 ± 1.0; p=0.02) compared to normotensive pregnancy (
Figure 1
). Similarly, corrected MPR remained significantly lower with prior preeclampsia versus uncomplicated pregnancy (2.36 ± 1.0 vs 3.36 ± 1.46; p=0.03).

Conclusions:
In this study, we observed significantly reduced coronary microvascular function following a pregnancy complicated by preeclampsia at least 5 years postpartum. Heightened cardiovascular risk factors may attenuate this association; however, these observations indicate that systemic microvascular dysfunction in preeclampsia also involves the coronary microcirculation. Further research is needed to better understand the timing and association of these microvascular changes concerning preeclampsia and later heart disease.
Abstract 4143314: Veteran Affairs Lipid Optimization Reimagined Quality Improvement Program (VALOR-QI) – A Dual Process Approach to Lipid Management in Patients with Atherosclerotic Cardiovascular Disease (ASCVD) at the Long Beach VA
Authors: Vu Kenny , Lee Sayana
Published: November 2024

Objectives:
Improve clinical pathways to impact atherosclerotic cardiovascular disease (ASCVD) management of Veterans through a Learning Healthcare System model of quality improvement designed to improve the management of dyslipidemia among those with high-risk ASCVD.

Methodology:
Long Beach VA (LBVA) is one of 50 VA sites participating in a national quality improvement initiative called the VALOR QI: VA Lipid Optimization Reimagined Quality Improvement Project. VALOR-QI is a collaborative project between the U.S. Department of Veterans Affairs (VA) and the American Heart Association (AHA) with the goal of positively impacting Veterans’ cardiovascular (CV) health. As part of the program, VA sites work with an AHA QI Consultant develop and deploy a local quality improvement plan to help overcome site specific barriers preventing Veterans from achieving optimal cholesterol levels.

At the LBVA, patients with LDL-C>70 and an ASCVD diagnosis are screened from a list generated by the health care provider. If a patient meets criteria, the health coach approaches the patient and begins working with them once a month over the phone or in person. During these meetings medication compliance and refills are reviewed, lifestyle goals or progress are reevaluated, and patients are reminded of upcoming appointments and labs.

Results:
Since October 2022, the LBVA VALOR-QI program has directly interacted with 277 patients who have a high ASCVD risk and LDL-C>70. Of those 277 patients, 84 patients (30%) have reached an LDL-C<70. As of June 2024, 16 patients have maintained their LDL-C<70 for more than 6 months. Patients that have participated since October 2022 have seen a 59% improvement in LDL-C and 50% of those patients have reached goal. The VALOR-QI program collaborates with 8 different primary care or heart failure clinics and some clinics have experienced up to 53% of patients reaching LDL-C<70.

Conclusions:
The VALOR-QI program at the LBVA has demonstrated the effectiveness of a dual process approach of 1) active health coaching – working directly with patients on lifestyle changes, medication management, and healthcare reminders and 2) collaborating with patients’ providers on intensifying medication or referring to pharmacy or cholesterol clinics.
Abstract 4143328: Safety of Direct current cardioversion without pre-cardioversion imaging in patients presenting post percutaneous left atrial appendage occlusion
Authors: Bahbah Ali , Witt Dawn , Casey Susan , Kapphahn-Bergs Melanie , Halvorson Emily , Abdelhadi Raed , Sengupta Jay
Published: November 2024

Background:
Direct current cardioversion (DCCV) carries a risk of stroke in atrial fibrillation (AF) patients. Hence, published guidelines for mitigating this risk with oral anticoagulation (OAC). There is no consensus agreement on the safest approach when cardioverting patients with left atrial appendage occlusion device in situ.

Aims:
We aimed to compare association of pre-DCCV imaging with safety and outcomes in patients with WATCHMAN™ undergoing elective DCCV for atrial arrhythmias (AA)

Methods:
This was a retrospective cohort study of patients who received DCCV for AA during follow up after LAAO procedure from 2016-2024 within a large health care system. Safety endpoint was freedom from stroke, all-cause mortality, device embolism, and systemic embolism within 30-days post DCCV. Significant peri-device leak (PDL) was defined as > 5mm on cardiac imaging.

Results:
A total of 119 patients were included, more females 70 (59%), with more than half (64 (54%)) receiving a first-generation WATCHMAN™ 2.5, while the rest had WATCHMAN FLX™. Median age at presentation was 77 years (72,82), BMI of 31 kg/m2 (26,37), average CHADSVASC score of 4.5 and HASBLED score of 3. There was a median duration of 10 months (3,21) between LAAO to presentation for DCCV .

Forty-four (37%) patients had pre-DCCV imaging, while 75 patients did not receive pre-procedural imaging. Between the two groups, there was no significant difference in OAC (VKA-antagonist/DOAC) usage prior to presentation (8 (18.6%) vs 12 (16.4%), P=0.9), with single antiplatelet therapy was the prevalent anti-thrombotic regimen. There was no significant difference in CHADSVASC, HASBLED, age, LVEF, or timing of presentation relative to the LAAO procedure. Higher percentage of patients were discharged on OAC post DCCV in the imaging cohort (13 (30.2%) vs 14 (19.4%), p=0.27), the difference was not significant. No Device related thrombus (DRT) nor significant PDL was detected on imaging. But non-significant PDL ranging from 2mm-4.7mm was found in 8 (18.1%) out of 44 patients who had imaging prior to DDCV. Safety endpoint was achieved in both cohorts with zero adverse events occurring during the 30 day follow up period post-DCCV.

Conclusion:
Elective cardioversion for atrial arrhythmias is safe in patients with WATCHMAN™. There were no post-DCCV stroke events in the overall cohort and no DRT identified in the pre-DCCV imaging subgroup. Further studies are needed to determine when pre-DCCV imaging is warranted in this population.
Abstract 4143358: Epicardial Adipose Tissue is a Better Predictor of Structural Remodeling and Atrial Fibrillation Recurrence than Body Mass Index
Authors: Chahine Yaacoub , Chamoun Nadia , Kassar Ahmad , Akoum Nazem
Published: November 2024

Background:
Body mass index (BMI), a measure of overall obesity, is associated with various cardiovascular conditions including atrial fibrillation (AF). Epicardial adipose tissue (EAT), a visceral type of adipose tissue, distinct from the subcutaneous adipose tissue, promotes AF arrhythmogenesis through proinflammatory properties and proximity to the myocardium. We sought to compare left atrial (LA) EAT volume with BMI, in their relationship to LA structural remodeling (LA volume and fibrosis) and AF recurrence following catheter ablation.

Methods:
EAT was assessed via cardiac MRI using the 3D Dixon sequence, and fibrosis was assessed using Late Gadolinium Enhancement (LGE) sequence in 127 AF patients (Panel A). Of this cohort, 101 patients underwent radiofrequency or cryoballoon catheter ablation and were followed for AF recurrence.

Results:
The mean age of the cohort was 64±11 years (30.7% female). The mean BMI was 29.7±6.6 kg/m
2
. LA volume index was 57.45±20.58 mL/m
2
, LA EAT index was 18.1±8.5 mL/m
2
, and the LA fibrosis was 18.0±7.9%. Compared to BMI, LA EAT index correlated better with LA volume index (LA EAT: R=0.452, p<0.001; BMI: R=−0.03, p=0.73). Similarly, LA EAT index, compared to BMI, correlated better with LA fibrosis (LA EAT: R=0.387, p<0.001; BMI: R=0.104, p=0.251) (Panel B). The ROC curve for the logistic regression model of LA EAT index in the prediction of AF recurrence had an AUC of 0.77 (95% CI 0.68-0.86, p<0.001) and showed an optimal cutoff value of 14.3 mL/m
2
to identify patients at risk of AF recurrence post-ablation. Whereas, the ROC curve for BMI in the prediction of AF recurrence post-ablation had an AUC of 0.56 (95% CI 0.44-0.68, p=0.33) (Panel C). Cox regression analysis showed LA EAT (HR = 1.089; 95% CI: [1.049–1.131], p < 0.001) to be an independent predictor of post-ablation AF recurrence.

Conclusion:
EAT quantified using cardiac MRI, a reproducible and widely accessible imaging parameter, is a better predictor of LA volume, fibrosis and AF recurrence after catheter ablation than BMI.
Abstract 4143359: Troponin as a Predictor for Diagnosis and as a Prognostic Marker for Cardiovascular Outcomes in Immune Checkpoint Inhibitor (ICI) related Myocarditis.
Authors: Pereyra Milagros , FARINA JUAN , Mahmoud Ahmed K. , Scalia Isabel , Awad Kamal , Kanaan Christopher , Tagle-Cornell Maria Cecilia , Novais Barbara , Koepke Laura , Kenyon Courtney , Herrmann Joerg , Arsanjani Reza , Ayoub Chadi
Published: November 2024

Background:
ICI-related myocarditis is challenging to diagnose and associated with adverse cardiovascular events and mortality. ICI therapy has also been associated with acute coronary events. There is limited data regarding cardiac troponin T (cTnT) and its association with these cardiovascular outcomes.

Methods:
All patients treated with ICI at a tertiary institution from 2011 to 2022 were identified, and the charts of those with cTnT measurements were reviewed. In patients with cTnT elevation (cutoff of >14 ng/L), if the Bonaca criteria for myocarditis were met, these patients were labeled as cTnT+/myocarditis+, otherwise as cTnT+/myocarditis-. Patients with non-elevated cTnT values were labeled cTnT-. Medical records were reviewed for baseline characteristics and long-term outcomes, including cardiac death, new heart failure (HF) diagnosis, and MACE (myocardial infarction, TIA/stroke, new HF diagnosis). Kaplan-Meier curves were created to plot the comparison between the three groups.

Results:
A total of 1669 cancer patients who received ICI therapy had post-ICI cTnT measurements. Mean age was 68.7±11.3, 58.3% were male, with follow-up at 1 year post ICI administration. Of these, 59 patients were cTnT+/myocarditis+, 1077 patients were cTnT+/myocarditis-, and 533 were cTnT-. Survival free of cardiac death, MACE and new HF diagnosis showed a graded response from worst in cTnT+/myocarditis+ patients and best in cTnT- patients; cTnT+/myocarditis- patients had a more favorable but still worse prognosis than cTnT- patients (Figure 1). A cTnT value of 95 ng/L was identified as the best cutoff for the diagnosis of ICI-related myocarditis (AUC 0.82, sensitivity 81.36%, specificity 81.62%). The optimal cTnT cutoff for cardiac death was 576 ng/L (0.70, sensitivity 72%, specificity of 61%) and for MACE 319 ng/L (AUC 0.61, sensitivity 70%, specificity of 52%).

Conclusion:
In cancer patients receiving ICI therapy cTnT elevations indicate a higher risk of MACE, HF, and cardiac mortality even in patients without myocarditis. Although worst outcomes are seen in those meeting diagnostic criteria for myocarditis.
Abstract 4143405: Clinical Features, Hemodynamics, and Outcomes of Pulmonary Hypertension in Adults with Coarctation of Aorta
Authors: Abdelhalim Ahmed , Goda Ahmed , Hsu Andrea , Egbe Alexander
Published: November 2024

Background:
Pulmonary hypertension (PH) and secondary right ventricle dysfunction is present in 20% of adults with coarctation of aorta (COA) based on echocardiographic studies. There are limited data about invasive hemodynamic characterization of PH in COA. The purpose of this study was to delineate the clinical features, hemodynamics, and outcomes of PH in COA.

Method:
Retrospective cohort study of adults with repaired COA that underwent right heart catheterization (RHC). PH was defined as pulmonary artery (PA) mean pressure >20 mmHg, and PH was classified as isolated precapillary PH and combined pre/postcapillary PH.

Results:
Of 99 COA patients that underwent RHC, 57 (58%) had PH. Of the patients with PH, 14 (25%) had isolated precapillary PH while 43 (75%) had postcapillary PH with or without precapillary disease. The correlates of PH were PA compliance (adjusted OR 0.79, 95% CI 0.71-0.86 per 1 ml/mmHg), left atrial reservoir strain (adjusted OR 0.95, 95% CI 0921-0.98 per 1%), and atrial fibrillation (adjusted OR 2.18, 95% CI 1.20-13.5). Higher PA mean pressure was associated with risk of cardiovascular events (adjusted HR 1.04, 95% CI 1.02-1.06 per 1 mmHg) and all-cause mortality (adjusted HR 1.05, 95% CI 1.02-1.08 per 1 mmHg).

Conclusions:
PH was present in over half of adults with COA referred for RHC, and one-quarter of the patients with PH presented with isolated precapillary PH suggesting an underlying PA vascular dysfunction as a contributing mechanism. Further studies are required to determine optimal therapies and strategies for prevention and treatment of PH in this population.
Abstract 4143426: Massage therapy for postoperative pain in patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials
Authors: Barbosa Lucas , Araujo Beatriz , Queiroz Ivo , Mendes Barbosa Julia , Ferreira Yasmin , Mesquita Cynthia
Published: November 2024

Background:
Massage therapy has been increasingly recognized as a complementary intervention that can help alleviate pain and anxiety in various clinical settings. However, the efficacy of this intervention in patients undergoing cardiac surgeries remains unclear. This systematic review and meta-analysis aims to evaluate the existing evidence of massage therapy for postoperative pain in cardiac surgery patients.

Methods:
We systematically searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) analyzing the efficacy of massage therapy in patients undergoing cardiac surgeries. We pooled standardized mean differences (SMD) for continuous outcomes with 95% confidence intervals (CI) with a random-effects model. We utilized mean change from baseline values and post intervention values in separated plots to preserve the weighting of this meta-analysis. We performed a trial sequential analysis (TSA) to assess the random risk of postoperative pain with mean change from baseline values. We used R version 4.3.2 and TSA version 0.9.5.10 for statistical analyses.

Results:
Our meta-analysis included 12 RCTs comprising 1015 patients, of whom 484 (47.7%) were randomized to massage therapy. Compared with control, massage significant reduced postoperative pain based on mean change from baseline values (SMD -0.47; 95% CI: -0.73 to -0.21; p<0.01; Figure A), and post intervention values (SMD -0.47; 95% CI: -0.82 to -0.12; p<0.01; Figure B). Additionally, massage therapy demonstrated a significant reduction in postoperative anxiety analyzing mean change from baseline values (SMD -0.46; 95% CI: -0.73 to -0.20; p<0.01; Figure C), and post intervention values (SMD -0.60; 95% CI: -0.94 to -0.26; p<0.01; Figure D). For the primary endpoint, TSA indicated a low risk of type 1 error, therefore this result may not be conclusive.

Conclusion:
In patients undergoing cardiac surgery, massage therapy significantly reduced postoperative pain and anxiety.
Abstract 4143433: Vascular Determinants of Functional Capacity in Peripheral Artery Disease
Authors: Sullivan Alexander , Behroozian Adam , Shardelow Emily , Smith Emily , Holder Tara , Wells Quinn , Aday Aaron , Wasserman David , Barnett Joey , Clair Daniel , Crescenzi Rachelle , Freiberg Matthew , Curci John , Garrard Clifford , Donahue Manus , Beckman Joshua
Published: November 2024

Background:
Patients with peripheral artery disease (PAD) experience walking impairment that is incompletely explained by conduit artery atherosclerotic occlusive disease and ankle-brachial index (ABI). Microvascular dysfunction is associated with adverse outcomes including amputation but its effect on ambulation is unknown. We tested whether calf skeletal muscle microvascular function independently associates with walking distance and with ambulatory improvement following exercise therapy or revascularization.

Hypothesis:
Calf skeletal muscle microvascular function predicts walking distance after adjusting for conduit artery function and ABI.

Methods:
Sixty-eight participants, including 50 with PAD (ABI
<
0.85) and 18 controls underwent vascular function assessment after sphygmomanometer cuff-induced calf ischemia using magnetic resonance imaging (MRI) measures of blood-oxygenation-level-dependent (BOLD) perfusion-dependent reactivity and arterial-spin labeling-based perfusion reactivity. Functional status was assessed using 6-minute walk testing (6MWT). A subgroup of PAD patients underwent repeat testing after exercise therapy (n=14) or revascularization (n=14). Multivariable regression models were used to assess the association of microvascular function with 6MWT distance controlling for age, sex, diabetes, ABI, and macrovascular function.

Results:
Resting conduit artery pressure by ABI (R=0.74, p<0.001), BOLD macrovascular reactive hyperemic blood flow (R=0.40, p<0.001), and skeletal muscle microvascular BOLD maximal reactivity (R=0.66; p<0.001) significantly correlated with 6MWT distance in univariable vascular testing (Figure 1A-C). In multivariable analysis of each vascular parameter, calf skeletal muscle microvascular reactivity most strongly associated with 6MWT (b=825.3, p=0.023). In those with repeat testing after intervention, the change in microvascular BOLD reactivity, but not ABI or macrovascular BOLD blood flow, significantly correlated with change in 6MWT distance (R=0.46, p=0.014, Figure 1D-F).

Conclusions:
Skeletal muscle microvascular function directly associates with walking distance independent of conduit artery blood flow and correlates with ambulatory improvement following PAD interventions.
Abstract 4143448: Obesity Prevalence Differs by Asian Ethnicity across the Adult Lifespan
Authors: Naidu Anika , Gordon Nancy , Ramalingam Nirmala , Njuguna Veronica , Shin Edward , Majid Inaya , Lo Joan
Published: November 2024

Background:
The US Asian population comprises diverse ethnic subgroups with distinct cultural and dietary profiles that influence their health outcomes. However, most research has focused on obesity trends among general populations, and little is known about trends within Asian ethnic subgroups. We examined the variation in obesity prevalence among the four largest US Asian subgroups in comparison with White, Black, and Hispanic groups across five age decades of the adult lifespan.

Methods:
This retrospective study used electronic health record data for 101,837 Filipino, 98,281 Chinese, 76,916 South Asian, 28,764 Vietnamese, 805,051 White, 124,412 Black, and 328,064 Hispanic adults aged 30-79y who were members of a Northern California health plan in 2019 and had a measured BMI. Obesity was defined as body mass index (BMI) ≥27.5 kg/m2 for Filipino, Chinese, South Asian, and Vietnamese adults and ≥30 kg/m2 for White, Black, and Hispanic adults. Obesity prevalence was compared by sex in Asian and non-Asian groups at ages 30-39y through 70-79y.

Results:
Among Asian men and women, obesity prevalence was consistently higher among Filipino and South Asian adults than among Chinese and Vietnamese adults (
Figure
). Obesity prevalence in Asian adults peaked at 58-59% for Filipino men at age 30-49y, 43-44% for Filipino women at 30-49y, and 42-46% for South Asian women at 50-69y. At age ≥40y, obesity prevalence was similar in South Asian and White men, whereas Filipino men tracked higher, in the range of Black and Hispanic men. For women, obesity prevalence was higher among Filipina than South Asian women under age 50y. However, this trend reversed in women age ≥50y, when prevalence was similar among Filipina and White women, and higher for South Asian women who tracked closer to Hispanic women. Black women had the highest obesity prevalence across all age decades.

Conclusion:
Across five age decades, obesity prevalence was substantially higher among Filipino and South Asian than Chinese and Vietnamese ethnic groups. These trends point to an alarmingly high obesity burden among Filipino and South Asian adults and underscores the importance of using disaggregated Asian ethnic subgroup data to study health risks and outcomes.
Abstract 4143465: Aortic Root Pressure for Detecting Aortic Stenosis using Machine Learning
Authors: Dunn Michael , Lalush David , Wheaten Sterling , Stouffer George , Syed Faisal
Published: November 2024

Background:
Aortic stenosis (AS) is a progressive, deteriorative valvular condition that is associated with significant morbidity and mortality. The best method to diagnose the severity of AS is controversial as all of the current modalities have multiple potential sources of error. As severity of AS increases, the time from aortic valve opening to peak systolic pressure increases. We hypothesized that machine learning applied to pressure measured in the aortic root via a fluid filled catheter at the time of cardiac catheterization would accurately diagnose aortic stenosis.

Aims:
Use a long-short term memory (LSTM) neural network to identify AS using aortic root pressure.

Methods:
We assessed aortic root pressure recordings in 102 consecutive patients undergoing transcatheter aortic valve replacement (TAVR) at our institution between 2014 and 2017. A LSTM was trained, validated, and tested using pre- and post- TAVR aortic root pressure 1 Hz digital recordings of 3.5 seconds duration. Recordings were selected to be artifact-free and in sinus rhythm. A 10-fold cross-validation structure was used (170 training, 17 validation, 17 testing tracings). The model was assessed using area under the receiver operating curve (AUROC) and F1 score.

Results:
The LSTM was able to distinguish between pre-TAVR (severe AS) and post-TAVR (no AS) tracings with sensitivity of 0.764, specificity of 0.703, AUROC of 0.792, and F1 score of 0.741. In comparison, when pressure tracings of the left ventricle were added to the model, the LSTM performance improved to sensitivity of 0.956, specificity of 0.950, AUROC of 0.977, and F1 score of 0.954.

Conclusion:
This proof-of-concept study demonstrated that aortic pressure alone can be used to detect severe AS. A larger analysis is needed to validate these findings across gradients of severity. This study has implications for using automatic AS severity assessments during cardiac catheterization to accurately diagnose AS.
Abstract 4143480: The Impact of Cardiac Rehabilitation Completion on Quality of Life, Social Support, Depression, and Chronic Pain
Authors: van Dover Timothy , Farbaniec Michael , SINOWAY Lawrence , Zehner Michael , Nudy Matthew
Published: November 2024

Background:
Social isolation and loneliness have been found to be associated with many chronic diseases including cardiovascular disease (CVD) and those with both CVD and social isolation may have a worse prognosis. Cardiac rehabilitation (CR) has been shown to improve outcomes following cardiac events. We hypothesize that CR may have beneficial impacts on quality of life, social support, depression, and pain rated via Dartmouth COOP Charts (COOP).

Research Question:
What is the impact of cardiac rehabilitation on quality of life, perceived social support, depression, and chronic pain?

Methods:
Data from Penn State Hershey Medical Center’s CR program was extracted pre-and post-CR, including Body Mass Index (BMI), Metabolic Equivalents (METs) performed, and components of COOP (social support, quality of life (QoL), depression, pain), with impairment rated from 1 to 5, with 5 representing worse impairment. Analysis was performed with paired t-test. Sensitivity analysis was performed including only high-risk participants (pre-rehab COOP score ≥ 3) for social support, depression, and pain as well as BMI ≥ 30 kg/m
2
.

Results:
A total of 743 participants were included with a mean (±SD) age of 66.3 (±11.3) years. CR improved METs performed, QoL, depression, and pain (Table 1). When analyzing all participants, CR did not improve social support or BMI. However, when only analyzing those with higher social support needs at baseline (n= 78) as well as elevated BMI ≥30kg/m
2
, CR was associated with improved social support and BMI. QoL, depression and pain also improved among the higher risk groups (Table 2).

Conclusion:
CR programs have demonstrated benefits for cardiovascular mortality and may have powerful impacts on patients’ mental health, pain, and social support. Further studies are needed to further elucidate the role CR may have in improving outcomes in participants with social isolation and loneliness.
Abstract 4143505: An Examination of Contextual and Self-Management Factors in Relation to Blood Pressure Control among Adults Managing Comorbid HIV and Hypertension in Malawi
Authors: Ogugu Everlyne , Bidwell Julie , Butterfield Rita , Ruark Allison , Neilands Torsten , Weiser Sheri , Mulauzi Nancy , Mkandawire James , Conroy Amy
Published: November 2024

Introduction:
Uncontrolled hypertension substantially increases the risk for cardiovascular disease and is a major cause of mortality among people living with HIV in many countries in sub-Saharan Africa, including Malawi. Despite previous studies showing low rates of blood pressure (BP) control among individuals with comorbid HIV and hypertension in these settings, few have focused on identifying potentially modifiable factors for improving BP control. This study examined contextual and self-management behaviors associated with BP control.

Methods:
This is a cross-sectional analysis of baseline data from participants in Healthy Hearts, a cohort study of persons with HIV and cardiometabolic conditions in Malawi. Participants were adults aged ≥18 years with HIV and hypertension (n=202), recruited from HIV care clinics at 3 hospitals. Multiple logistic regression was used to examine factors associated with BP control, defined as mean systolic BP <140mmHg and diastolic BP <90mmHg based on the 2020 International Society of Hypertension guidelines. Independent variables included age, gender, education level, access to healthcare, presence of comorbid conditions, body mass index, multimorbidity illness perceptions, hypertension-related knowledge, and self-management behaviors (self-reported physical activity, salt intake, fruit and vegetable intake, and antihypertensive medication adherence).

Results:
All participants were on antiretroviral therapy, 83.1% were on antihypertensive medication, and only 37.3% had controlled BP. Having a higher score in hypertension-related knowledge was positively associated with BP control (odds ratio [OR], 2.44; 95% CI 1.14–5.23). Factors negatively associated with BP control included increasing age (OR, 0.92; 95% CI 0.89–0.96), low antihypertensive medication adherence (OR, 0.32; 95% CI 0.11–0.89) or not being on antihypertensives (OR, 0.30; 95% CI 0.11–0.82), and perceiving multimorbidity as having greater negative impact on health (OR, 0.54; 95% CI 0.30–0.98).

Conclusions:
Age and potentially modifiable factors such as hypertension-related health literacy, medication adherence, and multimorbidity illness perceptions were independently associated with BP control at baseline in a cohort of Malawian adults with comorbid HIV and hypertension. These insights can help guide the development of tailored interventions for promoting BP control in persons with HIV at high risk for cardiovascular disease living in low-income countries.
Abstract 4143511: Association of Triglyceride Glucose-Related Parameters with All-cause mortality and Cardiovascular Disease in Non-alcoholic Fatty Liver Disease Patients
Authors: Chen Yaqin , Zhang Yusha , Wang Fengjiao
Published: November 2024

Background:
The Triglyceride-glucose (TyG) index , a novel indicator of insulin resistance, has been associated with mortality from non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). However, the association between the TyG index and the derived index of TyG (TyG-WHtR) and CVD in NAFLD patients remains unclear.

Methods:
This study enrolled 6627 adults aged 18 and above diagnosed NAFLD from the National Health and Nutrition Examination Survey (NHANES, 1999-2018). Binary weighted logistic regression analyses, cox proportional hazards model, restricted cubic spline (RCS), and receiver operating characteristic (ROC) were used to analyze the relationship between TyG and TyG-WHtR and all-cause mortality, CVD mortality and CVD related diseases. Mediation analysis explored the mediating role of glycohemoglobin (HbA1c), insulin and hypertension in the above relationships.

Results:
Except for no significant association between TyG and all-cause mortality and chronic heart failure (CHF), both TyG and TyG-WHtR exhibited significant positive correlations or trends of positive correlation with all-cause mortality, CVD mortality, total-CVD, CHF, coronary heart disease (CHD) and angina pectoris. For all-cause mortality, CVD mortality and CHF, TyG-WHtR was a better predictor than TyG (HR 1.31, 95%CI 1.03-1.66; HR 2.22, 95%CI 1.42-3.47; OR 3.99, 95%CI 1.79-8.93). However, TyG index demonstrated a stronger association with total-CVD, CHD and angina pectoris (OR 2.00, 95%CI 1.26-3.18; OR 1.85, 95%CI 1.19-2.91; OR 2.93, 95%CI 1.23-7.00). Otherwise, the ROC curve illustrated that, for all-cause mortality, CVD mortality, CHD and angina pectoris, TyG had a higher diagnostic efficacy. For CHF, the diagnostic efficacy of TyG-WHtR is higher. For total-CVD, TyG and TyG-WHtR had approximately equal diagnostic efficacy. RCS analysis showed that after adjusting for covariates, most of the above relationships were linearly correlated (P-overall < 0.0001, P-nonlinear> 0.05), while TyG and TyG-WHtR were non-linearly associated with all-cause mortality and CHF (P-overall < 0.0001, P-nonlinear< 0.05) in NAFLD patients.

Conclusions:
The predictive value of TyG or TyG-WHtR for mortality and cardiovascular risk in NAFLD patients was significant. The TyG index and TyG-WHtR might be a valid predictor of cardiovascular outcomes of patients with NAFLD.
Abstract 4143528: HeartMap: An Integrated Cell Atlas of 2.6 million cells across 260 individuals
Authors: Datar Yesh , Chaffin Mark , Simonson Bridget , Ellinor Patrick
Published: November 2024

Background:
Single-nucleus RNA sequencing (snRNA-seq) is a powerful tool to define the cell-type specific transcriptional signature in health and disease. Although it has been applied to study many forms of cardiovascular disease, few resources exist to compare results across studies and disease states.

Methods:
We identified 9 studies from the literature with > 10k nuclei, individuals > 18 years, and non-diseased controls. Existing data was downloaded, similarly re-processed, aligned to the GRCh38 reference transcriptome, and aggregated for quality control. Sixteen versions of data integration methods were benchmarked with the single-cell integration benchmarking (scIB) package. Clustering analysis was conducted in SCANPY using established methods to identify global cell types and distinct cell states within cell types. Cell type and cell state labels were assigned to clusters based on differential expression testing using limma-voom. Compositional analysis was conducted using scCODA.

Results:
HeartMap contains 2,600,078 cells across 36,601 genes from 9 studies, 260 individuals, 7 disease states and normal controls, and 8 anatomical regions. The median age was 54 years (IQR: 17) and 40% were female. Benchmarking selected single cell annotated variational inference as the optimal integration method. Global clustering of all nuclei revealed 14 major cell types. At the sample level, after controlling for differences between studies, the strongest sources of variation in transcription included disease status, patient sex, and anatomical region of sample. To demonstrate the utility of this resource, we identified 10 distinct fibroblast sub-populations among ~580,000 fibroblast cells. Two sub-populations of activated fibroblasts show POSTN+COL22A1+ and POSTN+TNC+ enrichment in primary (DCM/HCM) and ischemic (ICM/AMI/CAD) cardiomyopathies, respectively. Validation using RNA-scope and immunofluorescence staining revealed peri-vascular patterns of TNC+ fibroblasts and interstitial patterns of COL22A1+ fibroblasts in diseased tissues.

Conclusions:
HeartMap provides a unique resource to the cardiovascular research community and provides additional insights into the transcriptional diversity in health and disease.