bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4141127: Combined use of cardioprotective glucose-lowering drugs and statins in individuals with type 2 diabetes is associated with the lowest risk of all-cause mortality
Authors: Ternhamar Tummas , Johansen Mia , Nordestgaard Borge , Afzal Shoaib
Published: November 2024

Introduction:
Cardioprotective glucose-lowering drugs including sodium glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, and lipid-lowering statins are both aimed at preventing morbidity and mortality in individuals with type 2 diabetes. The importance of combining cardioprotective glucose-lowering drugs and statins in a real-world setting is unknown, and this was never tested in a 2-by-2 randomized trial.

Hypotheses:
We tested the hypothesis that combination of cardioprotective glucose-lowering drug and statin is associated with lower risk of all-cause mortality than using either drug alone.

Aims:
We investigated the association with all-cause mortality of combined treatment of cardioprotective glucose-lowering drug with statin versus either drug alone versus no drugs, in a nationwide real-world setting.

Methods:
From January 2013 through December 2021, we identified all individuals with type 2 diabetes living in Denmark. We categorized four groups according to treatment status: i) both cardioprotective glucose-lowering drug and statin, ii) cardioprotective glucose-lowering drug alone, iii) statin alone, and iv) neither cardioprotective glucose-lowering drug nor statin. First, using a simple cohort design, we followed 197,507 individuals with type 2 diabetes from January 2015 through December 2021. Second, using a time-varying cohort design, we followed all 354,979 individuals with type 2 diabetes and updated their treatment and covariate status annually from 2013 through 2021. All-cause mortality was assessed from the nationwide Danish Central Person Registry, which is 100% complete.

Results:
During mean follow-ups of 6.1 and 6.0 years, 50,571 and 80,712 individuals died in the simple and time-varying cohorts. Compared with nonusers of cardioprotective glucose-lowering drug or statin, the multivariable adjusted hazard ratios of all-cause mortality were 0.60 (95% confidence interval: 0.57–0.63) for combined use of cardioprotective glucose-lowering drug and statin, 0.76 (0.74–0.77) for treatment with statin alone, and 0.76 (0.70–0.82) for treatment with cardioprotective glucose-lowering drug alone. Corresponding values in the time-varying cohort were 0.43 (0.42-0.45), 0.63 (0.62-0.64), and 0.61 (0.58-0.64), respectively.

Conclusions:
In individuals with type 2 diabetes, treatment with a cardioprotective glucose-lowering drug and statin in combination was associated with a lower risk of all-cause mortality than using either drug alone.
Abstract 4141142: Environmental burden is associated with cardiometabolic risk factors in racially diverse breast cancer patients
Authors: Jung Wonyoung , Huang Anran , Bhattacharya Saveri , Fayanju Oluwadamilola , Knollman Hayley , Lattimer Jennie , Shah Payal , Clark Amy , Golec Sophia , Narayan Vivek , Isaacs Jordan , Koropeckyj-Cox Daniel , Hubbard Rebecca , Chen Jinbo , Levy Richard , Martei Yehoda , Ko Kyunga , Wilcox Nicholas , Smith Amanda , Yancy Clyde , Guerra Carmen , Powell-Wiley Tiffany , Ky Bonnie
Published: November 2024

Background:
The potential impact of neighborhood environment, a key structural social determinant of health, on disparities in cardiometabolic risk in cancer patients remains incompletely defined. We sought to determine the associations between environmental burden and cardiometabolic risk factors, and if these associations differed by race.

Methods:
Breast cancer patients initiating anthracycline and/or trastuzumab therapy at a multi-site health system were enrolled in a longitudinal prospective cohort study (NCT 05078190). At baseline, prior to cancer therapy initiation, neighborhood environment was defined by utilizing the Environmental Burden Module of the Environmental Justice Index from the CDC/ATSDR. The prevalence of cardiometabolic risk factors (hypertension, diabetes mellitus, dyslipidemia, obesity [BMI ≥30kg/m
2
], physical activity (PA) as defined by the Godin Leisure Time Questionnaire) was also ascertained. Sufficient PA was defined by a moderate-to-vigorous PA score ≥24. Age-adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression models.

Results:
Among 184 study participants (median [Q1-Q4] age 51 [43-60], 27.7% Black race), Black patients had greater (worse) environmental burden (0.83 [0.72-0.92]) compared to White patients (0.79 [0.46-0.87]). Patients with worse environmental burden were significantly less likely to meet sufficient PA levels (Q4 vs Q1 aOR 0.26, 95% CI 0.09-0.67), and more likely to have obesity (Q4 vs Q1 aOR 2.39, 95% CI 1.02-5.78). No significant associations were found with other cardiometabolic risk factors. In exploratory analysis stratified by race, associations between environmental burden and PA were more pronounced in Black patients, while associations between environmental burden and obesity were more pronounced in White patients (Table).

Conclusions:
Environmental burden was associated with PA and obesity in patients with breast cancer prior to the initiation of anthracycline and/or trastuzumab. Our findings motivate additional work in defining how environmental burden impacts cardiometabolic risk with cancer therapy longitudinally and disparities in cardiometabolic risk according to race.
Abstract 4141149: Atrial remodelling drives arrhythmia in Fabry Disease
Authors: Roy Ashwin , OShea Christopher , Cumberland Max , Holmes Andrew , Pavlovic Davor , Townend Jonathan , Geberhiwot Tarekegn , Gehmlich Katja , Steeds Richard
Published: November 2024

Background:
Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a-galactosidase deficiency, resulting in multi-organ accumulation of sphingolipid, namely globotriaosylceramide (Gb3). Gb3 accumulation triggers left ventricular hypertrophy, fibrosis, and inflammation, forming an environment for arrhythmia and sudden death, a common cause of FD mortality. Atrial fibrillation is common in FD and contributes to the high burden of stroke, yet the cellular mechanisms accounting for this are unknown. To address this, we conducted signal-averaged electrocardiography (ECG) analysis from a large cohort of adults with FD at varying stages of cardiomyopathy. Findings were compared with a novel human atrial model of FD, developed using gene-edited stem-cell derived atrial cardiomyocytes, exploring their molecular and functional properties.

Methods:
In 115 adults with FD, staged according to degree of cardiomyopathy, ECG P-wave characteristics were compared with non-FD age/sex-matched controls. Induced pluripotent stem cells were then genome-edited using CRISPR-Cas9 to carry the
GLA
p.
N215S
variant, the most common cardiac variant of FD in the UK, and differentiated into atrial cardiomyocytes (iPSC-CMs). Contraction, calcium handling and single-cell electrophysiology experiments were conducted to explore proarrhythmic mechanisms.

Results:
ECG analysis demonstrated P-wave duration and PQ interval shortening in FD adults with no cardiomyopathy compared with non-FD controls, which prolonged with cardiomyopathy stage. FD patients exhibited atrial dilation, high incidence of premature atrial contractions and increased risk of AF. In our cellular model,
GLA
p.
N215S
iPSC-CMs were deficient in a-Gal A and exhibited Gb3 accumulation.
GLA
p.
N215S
iPSC-CMs demonstrated a more positive diastolic membrane potential, a faster action potential upstroke velocity, a greater burden of delayed afterdepolarizations, greater contraction force, slower beat rate and significant dysfunction in calcium handling compared to WT iPSC-CMs. The identified ECG changes may be partly explained by our observed cellular changes.

Conclusions:
These findings enhance our understanding of atrial myopathy in FD by providing novel insights into underpinning mechanisms for atrial arrhythmia as well as rationale for early identified P-wave changes in FD. Mechanisms identified in this study may be targeted in future research to develop therapeutic strategies to reduce the atrial arrhythmic burden in FD.
Abstract 4141151: Coronary Artery Disease Polygenic Risk Scores with Equivalent Performance Produce Discordant Estimates of Individual Risk
Authors: Abramowitz Sarah , Boulier Kristin , Keat Karl , Cardone Katie , Shivakumar Manu , Depaolo John , Judy Renae , Kim Dokyoon , Ritchie Marylyn , Voight Benjamin , Pasaniuc Bogdan , Levin Michael , Damrauer Scott
Published: November 2024

Background:
Dozens of polygenic risk scores (PRSs) have been developed to estimate coronary artery disease (CAD) risk. Some are available clinically. PRS performances are traditionally evaluated and compared at the population level. Whether they provide similar individual-level assessments of disease liability is a critical consideration for clinical implementation that remains uncharacterized.

Research Question:
How does individual-level risk prediction compare across CAD PRSs?

Methods:
Published CAD PRSs were curated from the PGS Catalog, and two novel PRSs were created from the results of a large GWAS meta-analysis. For each score, normalized individual risk scores were calculated for All of Us Research Program (AOU) participants. PRSs with equal population-level performance were identified by using Bayesian analysis of variance to compare calibration and discrimination (Brier score and AUROC) of generalized linear models of prevalent CAD. Among equivalently performing scores, the individual-level agreement between risk percentile estimates was tested with intraclass correlation (ICC) and Light’s Kappa. This approach was replicated in the Penn Medicine Biobank (PMBB) and UCLA ATLAS Biobank.

Results:
50 PRSs were calculated for 171,095 AOU participants. When included in a model of prevalent CAD, 48 scores had practically equivalent Brier scores and AUROCs (region of practical equivalence = 0.02). Across these scores, 84% of AOU participants had at least one score in both the top and bottom risk quintile. Continuous agreement of individual risk predictions from the 48 scores was poor, with an ICC of 0.351 (95% CI; 0.349, 0.352). Agreement between two statistically equivalent scores was moderate, with an ICC of 0.646 (95% CI 0.643, 0.649). Light’s Kappa, used to evaluate consistency of assignment to high-risk percentile cutoffs, did not exceed 0.56 (interpreted as ‘fair’) across statistically and practically equivalent scores. Repeating the analysis among 41,193 PMBB and 50,748 UCLA participants yielded different sets of statistically and practically equivalent scores which also lacked strong individual agreement.

Conclusions:
When tested across three diverse biobanks, CAD PRSs that performed equivalently at the population level produced highly variable individual estimates of risk. Approaches to clinical implementation of CAD PRSs need to consider the potential for discordant individual risk estimates from otherwise indistinguishable scores.
Abstract 4141158: Weekend Effect on In-Hospital Outcomes of Transcatheter Aortic Valve Replacement: Insights from a Propensity-Matched National Analysis
Authors: Shi Bo , Ma Xueping , Jia Shaobin , Cong Guangzhi , Ye Congyan , Yan Rui , Fu Shizhe , Li Haowei , He Baotong , He Zefeng , Rehman Abdul , GITANGAZA Israel
Published: November 2024

Background:
The "weekend effect" on hospital admissions has been extensively studied, showing increased risks for patients admitted on weekends than those admitted on weekdays. We aimed to assess the “weekend effect” on in-hospital outcomes in patients undergoing transcatheter aortic valve replacement (TAVR).

Methods:
A nationwide cohort study was conducted using the National Inpatient Sample Database. We identified 82,094 eligible patients aged ≥ 18 years admitted for TAVR between 2013 and 2021. Patients were grouped into weekend or weekday cohorts based on day of admission. Propensity score matching (PSM) and multivariate regression models were employed to evaluate outcomes. After PSM, 2,688 weekend admissions and 13,440 weekday admissions were included in the analyses.

Results:
Multivariable regression, adjusted for propensity score, revealed that weekend admission was associated with 45% higher odds of in-hospital mortality (adjusted odds ratio: 1.45; 95% confidence interval: 1.13–1.85). Significant heterogeneity in mortality was observed based on admission urgency, with a 3.27 times higher increased risk of death observed for elective admissions on weekends than on weekdays (P for interaction = 0.001). Moreover, weekend admissions had significantly higher adjusted odds for cardiogenic shock, permanent pacemaker implantation, endocarditis, acute kidney injury, acute ischemic stroke, and blood transfusion. There was a trend of higher in-hospital mortality for weekend over weekday admissions throughout the study period.

Conclusions:
Weekend admissions for TAVR had higher mortality, complications, and resource utilization, particularly in elective cases. Our findings suggest that patients admitted for TAVR during weekends are at high risk and warrant special attention.
Abstract 4141159: Trends in Obesity Related Ischemic Heart Disease Mortality Among Adults in the United States from 1999 to 2020
Authors: Sohail Muhammad Umer , Saad Muhammad , Arshad Muhammad Sameer , Sohail Muhammad Ovais , Ahmed Aymen , Azhar Aima , Kumar Pankaj , Memon Muhammad , Shahid Izza
Published: November 2024

Background:
Obesity is a significant risk factor for ischemic heart disease (IHD) with increasing prevalence denoted in the recent decade. This study examines the temporal trends in obesity-related IHD mortality in the U.S. from 1999 to 2020.

Methods:
We used Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) Multiple cause of death database to analyze obesity related IHD mortality in adults ≥ 25 years old. We examined IHD as the underlying cause and obesity as a contributing cause. Age-adjusted mortality rates (AAMRs) and Crude mortality rates (CMRs) per 100,000 persons were calculated. Joinpoint regression was used to assess the trends and calculate annual percent change (APC) to examine trends overall, and across demographic (age, sex, race) and geographic regions.

Results:
A total of 139,644 obesity-related IHD deaths were identified. Overall, AAMR increased from 1.92 in 1999 to 4.69 in 2020. AAMRs showed a consistent rise between 1999 and 2018 (APC: 4.00 [95% CI: 2.85 to 4.44]), followed by a marked increase from 2018 to 2020 (APC: 9.87 [95% CI: 4.46 to 12.75]). AAMR was higher in males (3.79) than females (2.10). Black populations had the highest AAMR (4.06), followed by White populations (2.08) and Hispanic/Latino populations (1.94). Older adults (age 65+ years old) had the highest CMR (5.73), followed by middle-aged adults (age 45-64 years old, CMR: 4.31) and young adults (age 25-44 years old, CMR: 0.73). AAMR was higher in nonmetropolitan areas (3.47) compared to metropolitan areas (2.78). States in the top 90th percentile for AAMR were Vermont, Oklahoma, California, North Dakota, and Colorado, while those in the bottom 10th percentile were South Carolina, Massachusetts, Utah, Connecticut, and Alabama.

Conclusion:
Obesity-related IHD has increased drastically in the U.S. throughout the study period. Further research is needed to comprehend these trends and to help develop preventative tactics.
Abstract 4141173: CMR can discriminate need for biopsy and rejection therapy in children post heart transplant
Authors: Vegulla Ravi , Ceneri Nicolle , Richmann Devika , Mouzakis Nicholas , Hamman Karin , kanter joshua , Berger John , Downing Tacy , Loke Yue-Hin , Staffa Steven , Zurakowski David , Cross Russell , Olivieri Laura
Published: November 2024

Background:
Heart transplantation remains definitive therapy for children with heart failure, but the burden of acute graft rejection remains. While adult data has shown cardiac magnetic resonance (CMR) offers reliable, non-invasive identification of graft rejection1-3, endo-myocardial biopsy (EMB) continues to be the gold-standard in children.

Hypothesis:
CMR can establish the presence/absence of rejection, guiding need for EMB and rejection therapy.

Aims:
To assess the (1) strength of CMR parametric mapping in discriminating presence of rejection (defined as need for new therapy), and (2) the ability of CMR to identify patients without rejection, negating the need for EMB.

Methods:
Pediatric heart transplant patients referred for EMB underwent concurrent noncontrast CMR with volumetry, flows, MOLLI T1 and T2 parametric mapping at 1.5T. Average and peak segmental native T1 and T2 were measured in 6 slices, and regions of sub-segmental ‘hotspot’ elevation (3 continuous voxels T1>1050 ms or T2>60 ms) were identified. Rejection treatment was per institutional protocol, blinded to CMR results, categorized as (A)new IV therapy, (B)oral augmentation of maintenance, or (C) no change. Sensitivity, specificity and ROC analyses were performed.

Results:
95 encounters in 34 patients (median age 13.1y (IQR 7.5-16.3), BSA 1.37 m2 (1.1-1.6), 47% female) were completed, with treatment groups A 13%, B 5%, and C 82%. Significantly higher T1 and T2 values were found in the rejection groups. ROC curve analysis identified elevated peak T1 levels as the strongest predictor of rejection (AUC = 0.848, 95% CI: 0.746, 0.950, p<0.001), with optimal cutoff T1 >1099 ms. Subsegmental hotspots were present in all encounters with rejection requiring new therapy (100% sensitivity), however the type/ number of hotspots did not correlate with rejection. New rejection therapy was not initiated in any patient encounter without hotspots (NPV 100%).

Conclusions:
Elevated segmental T1 CMR values can identify children with graft rejection, and absence of subsegmental hotspot elevations can reliably identify patients without rejection. CMR is a promising non-invasive test to aid in graft surveillance and direct invasive testing and therapy.
Abstract 4141180: Opportunistic assessment of cardiovascular risk using deep learning of the heart and aorta on non-contrast chest computed tomography
Authors: Raghu Vineet , Sturniolo Audra , Kiel Douglas , Aerts Hugo , Natarajan Pradeep , Lu Michael
Published: November 2024

Purpose:
Primary prevention of cardiovascular (CV) disease relies on accurate risk estimation. The coronary artery calcium score (CAC) can be measured on routine chest computed tomography (CT); however, it is unclear whether the heart and thoracic aorta regions on CT can provide additional information about future risk beyond calcium and risk factors.

Methods:
We applied the open-source TotalSegmentator tool to extract heart and thoracic aorta volumes from 27,943 non-contrast non-ECG gated chest CTs from 17,241 National Lung Screening Trial participants. We used the segmented volumes from 10,356 participants as input to train a new 3D Densenet169 deep learning model to predict 12-year CV mortality. Independent testing was performed in 5,165 individuals not used for model training with no history of type 2 diabetes, myocardial infarction, or stroke (eligible for primary prevention). The deep learning score was compared to a regression model using demographics, smoking, BMI, comorbidities, and the radiologist’s findings from the CT. We stratified the CAC and deep learning scores into high vs. low-risk groups using a CAC>100 and deep learning >10% risk threshold, respectively.

Results:
In the independent testing dataset, (N=5165; median age 60.0±8.0 years; 62.6% male), 3.3% died of CV disease. The deep learning score had higher discrimination for CV mortality than risk factors and CT findings (deep learning AUC 0.72 [0.68,0.76] vs. baseline AUC 0.66 [0.61,0.69], p < 0.001). Similar results were found for secondary outcomes of fatal myocardial infarction and fatal stroke. In a subset of 2,972 testing set individuals with measured CAC, those with high CAC and a high deep learning score had a 10.8% rate of 12-year CV mortality, higher than those with high CAC alone (4.1%, p<0.001).

Conclusion:
Based on the heart and thoracic aorta regions from CT, a deep learning model predicted 12-year CV mortality beyond prevalent risk factors, CAC, and imaging findings.

Clinical Relevance:
Opportunistic screening of chest CT using deep learning may enhance risk assessment to guide decisions for preventing CV events. External validation in population-representative cohorts is needed before clinical use.
Abstract 4141198: Serum Homoarginine is a Strong Predictor of Cardiovascular Mortality in Patients with Chest Pain and Non-Obstructive Coronary Artery Disease
Authors: Storesund Silje Kjellevold , McCann Adrian , Ueland Per Magne , Lonnebakken Mai Tone , Nygard Ottar , Pedersen Eva
Published: November 2024

Introduction:
As substrates for nitric oxide, arginine (Arg) and its metabolites are involved in the regulation of vascular function. Ischemia caused by vascular dysfunction is common in patients with non-obstructive coronary artery disease (NOCAD) and may indicate a subgroup at increased risk of cardiovascular disease (CVD) mortality.

Research question:
We evaluated serum arginine (Arg), homoarginine (hArg), symmetric dimethylarginine (SDMA), and asymmetric dimethyl arginine (ADMA) as long-term predictors of CVD mortality in patients with chronic coronary syndrom. Particularly, we were interested in potential effect modifications according to diagnoses of NOCAD versus obstructive coronary artery disease (OCAD) at baseline invasive coronary angiography (ICA).

Methods:
4164 patients underwent elective ICA from 2000-2004. Serum metabolite concentrations were measured by liquid chromatography-tandem mass spectrometry using isotope labelled internal standards. Metabolite associations with CVD mortality risk were explored by Cox regression adjusting for age, sex, body mass index, HbA1c, hypertension, smoking status, serum LDL cholesterol, previous myocardial infarction, and estimated glomerular filtration rate. HRs (95% CI) are reported per SD increment of (log transformed) metabolites. Potential effect modifiers were evaluated by adding interaction terms to the model.

Results:
Median age was 62 years at inclusion. 72 % were men, 25 % had NOCAD, while 75 % had OCAD. During median 14 years of follow-up, 14 % of patients died from CVD. In multivariable analyses, serum concentrations of Arg, hArg and SDMA predicted CVD mortality with HRs (95% CI) of 0.90 (0.83-0.98), 0.81 (0.74-0.88) and 1.30 (1.12-1.50), respectively. Serum hArg was a significantly stronger inverse predictor in patients with NOCAD than in OCAD with HR (95% CI) of 0.54 (0.40-0.73) versus 0.84 (0.77-0.92), respectively (Pint = 0.037). No significant effect modifications were observed for the other arginine form (Pint ≥ 0.09).

Conclusion:
In patients with stable chest pain, Arg, hArg and SDMA significantly predicted long term CVD mortality. Interestingly, hArg was a stronger inverse predictor among NOCAD compared to OCAD patients. Further studies investigating hArg as a potential marker of a high-risk phenotype in NOCAD are merited.
Abstract 4141230: Systemic Sirolimus Therapy is Associated with Reduced Intervention Frequency in Pediatric Pulmonary Vein Stenosis
Authors: Kalustian Alyssa , Hagan Joseph , Brlecic Paige , Iacobas Ionela , Vanderlaan Rachel , Burns Joseph , Wu Thao , Birla Ravi , Gowda Sharada , Bansal Manish , Gowda Srinath , Eilers Lindsay , Khan Asra , Sandoval-Jones Juan Pablo , Imamura Michiaki , Orr Yishay , Caldarone Chris , Qureshi Athar
Published: November 2024

Background:
Pediatric pulmonary vein stenosis (PVS) has a guarded prognosis and often necessitates repeated interventions. Small retrospective studies suggest benefits to adjunctive enteral systemic sirolimus therapy (SST) for PVS, including improved survival, slowed progression of in-stent stenosis, and reduced frequency of catheterization procedures.

Hypothesis:
We hypothesized patients undergo PVS interventions less frequently while receiving SST compared to pre-SST.

Aims:
The principal aim was to determine the impact of systemic sirolimus therapy on PVS intervention frequency.

Methods:
We retrospectively identified 45 patients treated at Texas Children’s Hospital who completed >1 month of SST for PVS between 2015-2022. First course of SST was analyzed. Primary endpoint was PVS intervention frequency (number of surgical or transcatheter PVS interventions/year), calculated for two intervals per patient: pre-SST (PVS diagnosis until start of SST) and on-SST (start of SST until cessation or follow-up if no interruptions >1 month). Generalized Poisson mixed linear models were fit to test the impact of SST on intervention frequency, accounting for paired intervals within each patient. A multivariable model also included age at interval start, PVS type (primary/post-repair), sex, prematurity, and concurrent antiproliferative medications. Mean cumulative functions were also compared.

Results:
Median per-patient PVS intervention rate (interventions/year) was 5 (IQR 2.3-10.6) pre-SST and 1.7 (0.8-2.8) on-SST. PVS intervention rate was significantly lower on-SST compared to pre-SST by the univariable and multivariable Poisson models (P<.0001, both). Patients accrued an increased mean cumulative number of interventions over time pre-SST compared to on-SST (P<.0001, Figure). Median duration of SST was 1.7 years and follow-up time from SST initiation was 2.7 years. There were 6 mortalities with 90% (95% CI 75-96%) Kaplan-Meier estimated survival 2 years from SST initiation.

Conclusions:
SST was associated with a reduction in PVS intervention frequency. Prospective studies are warranted to determine potential causality, delineate patient and vein-level outcomes, and determine optimal therapeutic duration.
Abstract 4141238: HIV, Longitudinal Blood Pressure Trajectory, and Preclinical Echocardiographic Measures of Cardiovascular Disease in Tanzania: A Comparative Prospective Cohort Study
Authors: Roberts Nicholas , Ruselu Grace , Kisigo Godfrey , Willkens Megan , Cichowitz Cody , Desderius Bernard , Lee Myung Hee , Peck Robert
Published: November 2024

Background:
Longitudinal blood pressure (BP) trajectories are associated with cardiovascular disease (CVD) but have not been characterized in a sub-Saharan African (SSA) cohort. We identified distinct BP trajectories and evaluated their association with HIV and preclinical CVD.

Research question:
Is HIV associated with lower or higher BP trajectory in SSA? Is BP trajectory associated with preclinical CVD, and does HIV change the association?

Methods:
Our longitudinal cohort study included 437 people with HIV (PWH) and 473 HIV-uninfected adults recruited from public HIV clinics in Mwanza, Tanzania. Echocardiography was performed in 772 participants. Group-based multi-trajectory modeling identified trajectories based jointly on systolic and diastolic BP. Multivariable multinomial logistic regression determined the association between HIV and BP trajectory group. Multivariable linear regression evaluated the association between BP trajectory group and echocardiographic measurements, including average E/e’, left atrial volume index (LAVI), and left ventricular mass index (LVMI).

Results:
The mean age was 36 years and 68% (N = 623) were female. Four BP trajectories were identified (Figure 1), numbered from group 1 (lowest BP) to group 4 (highest BP). Compared to BP trajectory group 2, PWH had higher odds of being classified to group 1 (aOR: 1.71; 95% CI: 0.97-3.02) and lower odds of being classified to group 3 (aOR: 0.51, 95% CI: 0.36-0.71) and group 4 (aOR: 0.45, 95% CI: 0.29-0.71). Participants in group 4 had significantly higher average E/e’, LAVI, and LVMI compared to group 2 (Figure 2). The association between BP trajectory and preclinical CVD did not differ by HIV status. HIV was associated with higher LAVI and LVMI after adjusting for age, sex, traditional CVD risk factors, and BP trajectory.

Conclusion:
BP trajectory and HIV were independently associated with preclinical CVD. Integrating CVD prevention with routine HIV care is urgently needed in HIV clinics across SSA.
Abstract 4141243: All That Blocks is Not Clot: A Case of Left Ventricular Assist Device Obstruction from Extrinsic Compression
Authors: Waller Jamnius , Zhang Suyu , Agusala Veena , Guynn Nicole , Fernandez Timothy , Attia Tamer
Published: November 2024

Description of Case:
A 36-year-old male with a history of non-ischemic cardiomyopathy status post HeartMate 3 left ventricular assist device (LVAD) presented with a 2-day history of dizziness, lightheadedness, chest pain, and an increase in low flow alarm frequency from his LVAD. On admission, his temperature was 37.2, return to flow was 86, oxygen saturation was 100% on room air, heart rate was 99, and respiratory rate was 23. His lungs were clear to auscultation, and his abdomen was distended, tense, and non-tender. His extremities were warm, with moderate edema in his legs bilaterally. He had mild increased work of breathing without accessory muscle uses. Laboratory evaluation revealed a prothrombin time of 2.6 seconds, a B-type natriuretic peptide level of 176 pg/mL, and a hemoglobin of 13.7 g/dL. Imaging revealed a chest CT demonstrating a complete obstruction of the distal outflow cannula near its attachment to the aorta. Patient hemodynamics worsened after admission, necessitating transfer to the cardiac intensive care unit. After an unsuccessful attempt at warfarin reversal and tissue plasminogen activator administration, the patient was eventually taken for surgical intervention with cardiothoracic surgery. During the procedure, there were no signs of outflow graft thrombus; instead, a sizeable peri-graft fluid collection was observed and drained, which relieved the outflow graft obstruction. The patient’s post-operative course was uneventful, and he was eventually discharged home with a resolution of his symptoms.

Discussion:
This patient's presentation presents a few key features that suggest an alternative cause of an outflow obstruction other than an acute thrombus. The most important feature is that the patient had been diligent with his anticoagulation to indicate his being a therapeutic prothrombin time on admission, consistent with the patient's reported anticoagulation adherence. We believe that cases such as this one provide clinical support for the reevaluation of the way we approach outflow tract obstructions in LVADs; especially as we continue to develop devices that have lower thrombus risk that their predecessors. We hope that this patient’s clinical presentation and course will be helpful in the future differentiation of intrinsic vs extrinsic compression of LVAD cannulas and the management of such obstructions.
Abstract 4141244: RNA interference versus antibody-based PCSK9 inhibition for the prevention of cardiovascular disease: A drug-target Mendelian randomization study
Authors: Gagnon Eloi , Gill Dipender , Bourgault Jerome , Gobeil Emilie , Mitchell Patricia , Girard Arnaud , Paulin Audrey , Couture Christian , Bosse Yohan , Theriault Sebastien , Mathieu Patrick , Vohl Marie-Claude , Tchernof Andre , Ray Kausik , Kastelein John , Arsenault Benoit
Published: November 2024

Background and Aims:
RNA interference therapy targeting the proprotein convertase subtilisin/kexin type 9 (
PCSK9
) gene lower low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) levels and is approved worldwide. As opposed to monoclonal antibodies neutralizing PCSK9 in the circulation, their effect on atherosclerotic cardiovascular disease (ASCVD) outcomes is unknown. We used drug-target Mendelian randomization (MR) to assess the potential impact of RNA interference therapies targeting
PCSK9
on cardiometabolic traits and outcomes.

Methods:
We performed RNA-sequencing of 246 liver samples and genome-wide genotyping was performed to identify single-nucleotide polymorphisms (SNPs) associated with liver expression of
PCSK9
. Genome-wide association study (GWAS) summary statistics of plasma protein levels of PCSK9 from the deCODE study (n=35,559) were used to instrument inhibition of circulating PCSK9 levels. A three-sample MR approach was undertaken using SNPs that influence liver
PCSK9
gene expression levels (mimicking PCSK9 RNA interference) or plasma PCSK9 protein levels (mimicking PCSK9 neutralizing antibodies) as study exposures. Genetic instruments were standardized for their effect on apoB levels. Main outcomes measures included GWAS summary statistics on coronary artery disease (CAD), ischemic stroke (IS) and type 2 diabetes (T2D).

Results:
Each SD decrease in apoB was linked with a 55% and 56% reduction in CAD risk, respectively for genetically predicted reductions in plasma PCSK9 levels (OR [odds ratio]=0.45 [95% CI], 0.36-0.56, p=1.7e-13) and liver
PCSK9
gene expression levels (OR=0.44 [95% CI], 0.22-0.88, p=0.02). Genetically predicted reductions in plasma PCSK9 levels and liver
PCSK9
gene expression levels were associated with slightly lower IS risk (OR=0.82 [95% CI], 0.68-0.98, p=0.03 and OR=0.73 [95% CI], 0.51-1.04, p=0.08, respectively). Genetically predicted reductions in plasma PCSK9 levels and liver
PCSK9
gene expression levels were not associated with T2D risk (OR=1.08 [95% CI], 0.92-1.28, p=0.34 and OR=1.26 [95% CI], 0.93-1.71, p=0.14, respectively). The effect of PCSK9 inhibition on CAD was entirely mediated by reductions in apoB levels.

Conclusions:
Genetically predicted reductions in plasma PCSK9 levels and liver
PCSK9
gene expression levels were associated with lower ASCVD risk, suggesting that LDL-C/apoB reductions may provide cardiovascular benefits, regardless of how PCSK9 function is inhibited.
Abstract 4141265: Single Center Utilization of Prenatal Palliative Care in Patients with Critical Congenital Heart Disease: Missed Opportunities?
Authors: Tredway Hannah , Moynihan Katie , Bloomhardt Hadley , Snaman Jennifer , Purol Nicholas , Hoganson David , Ronai Christina
Published: November 2024

Background:
Congenital heart disease (CHD) is a common congenital anomaly with lesions requiring intervention before initial hospital discharge defined as critical CHD (CCHD). Advances in prenatal detection, surgical, and post-operative care have improved early survival of patients with CCHD, yet long-term survival is limited. Fetal echocardiography has improved diagnosis and characterization of CCHD, and prenatal palliative care (PC) consult can improve shared decision making, communication, and parental stress of patients with life-limiting conditions. We hypothesized that the utilization of prenatal PC consults for patients with CCHD would be low (<10%).

Methods:
Descriptive patient series of prenatal CCHD diagnosess at Boston Children’s Hospital from January 2020-December 2023. CHD type, prenatal characteristics, mode of delivery, cardiac interventions, intubations, mechanical circulatory support, timing of PC consult, and survival or mechanism of death were collected and analyzed. Early PC consult was defined as prenatal or occurring more than 30 days prior to death. Mode of death and age at death were compared between early, late, and PC.

Results:
603 patients had a prenatal diagnosis of CCHD. 23% (n=141) had single ventricle heart disease. 10% (n=62) had a PC consult, only 4.8% (n=3) were performed prenatally. Median age at PC consult was 143 days [31 wks gestation, 4 yrs]. 8% (n=49) died, with a median age at death of 57 days [IQR 13, 171]. The majority of patients (65%, n=31) died following discontinuation of life-sustaining treatment, 29% (n=14) died following treatment limitation (TL), and 17% (n=8) underwent unsuccessful resuscitation. Of the deceased patients, 63% (n=31) had a PC consult
.
Early PC consult occurred in 33% (n=15) of deceased patients. Early PC consult was significantly associated with an older age at death (255 +/- 180 days), in comparison to late or no PC consult (69 +/- 77 days, 88 +/- 196 days). Patients with early PC consults were less likely to die following active resuscitation or TL (20%, n=3) than those with late or no PC consult (57%, n=8, 33%, n=6 respectively, p < 0.05).

Discussion/Conclusion:
Patients with CCHD experience significant morbidity and mortality. Despite the known support that PC provides in decision making, establishing goals of care, and providing an extra layer of longitudinal support for families, early integration of PC upon prenatal diagnosis of CCHD is infrequently utilized at our institution.
Abstract 4141272: Trends in Cancer Versus Cancer with Heart Failure Related Mortality in the United States from 1999-2020. A CDC WONDER Database Analysis
Authors: Ahmed Faizan , MIRZA TEHMASP , Patel Brijesh , Naveed Muhammad Abdullah , Abdul Basit Salman , Ali Farman , Ishaq Syed , Akbar Usman , Haider Mobeen , sattar yasar , Khosa Faisal
Published: November 2024

Aims:
This study aimed to analyze two decades of consecutive mortality data to investigate the association between cancer and cancer with heart failure across the United States (US), discerning patterns and disparities in mortality rates.

Methods:
Data were obtained from the multiple cause of death files using CDC WONDER spanning 1999 to 2020; ICD-10 codes were used to identify cancer and cancer with heart failure related deaths in adults aged ≥25. Demographic and regional distributions of mortality were analyzed. Joinpoint regression analysis was used to determine trends in age-adjusted mortality rates (AAMR) to estimate annual percentage changes (APC).

Results:
Between 1999 and 2020, 14,309,991 cancer-related deaths occurred in the US out of which 612,346 were associated with cancer and heart failure. The overall AAMR per 100,000 for cancer-related deaths decreased from 353.9 in 1999 to 260.9 in 2020 characterized by an annual percentage change (APC) of -1.60 spanning from 1999 to 2018, and an APC of 0.58 thereafter till 2020. AAMR per 100,000 for heart failure and cancer-related deaths decreased from 16.1 to 14.0, with varied APCs, declining from 1999 to 2013, reaching a minimum AAMR of 11 followed by a rise from 2013 to 2020. For cancer related only, men accounted for 52.7% of deaths, compared to 47.3% for women. Similarly, cancer with heart failure had mortality higher in males. Non-Hispanic (NH) White and Hispanic populations had the highest AAMRs for cancer related mortality while NH White and NH American Indian or Alaskan Native had the highest mortality in cancer with heart failure. Regional differences were observed, with the most cancer-related deaths observed in the South while the most cancer with heart failure related deaths occurred in the Midwest. State-wise stratification further supported the difference.

Conclusions:
Cancer-related mortality is decreasing while cancer with heart failure related mortality is increasing following initial decline. The highest AAMRs were observed for cancer related mortality among NH White population, men, people living in the South; and non-metropolitan US while cancer with heart failure had highest mortality in NH White population, men, people living in Midwest; and non-metropolitan areas. The findings underscore the need for focused interventions aimed at reducing mortality related to cancer and cancer with heart failure, particularly among vulnerable populations.
Abstract 4141279: Catch me if you flow slow: The temporal filter slow flow fact
Authors: Kanegawa Munehiro , Kagawa Eisuke
Published: November 2024

Background:
Slow flow phenomenon is impaired coronary flow during percutaneous coronary intervention (PCI) in absence of mechanical obstruction, and it is associated with deteriorated outcome. Filter device may prevent final slow flow; however, the impact of slow flow phenomenon with an intra-coronary filter device for STEMI is unclear.

Objectives:
We assessed the hypothesis that temporal filter slow flow (FSF) during procedures of reperfusion therapy end in Thrombolysis in Myocardial Infarction flow grade 3 (TIMI-3) in STEMI is not associated with myocardial infraction size, using cardiac magnetic resonance (CMR).

Methods:
STEMI patients who underwent coronary revascularization therapy and cardiac magnetic resonance (CMR) at about 4 days and 6 months between 2017 and 2023 were included. The patients were divided into groups (Group 1, FSF (-) during procedures with final TIMI-3; Group 2, FSF (+) with TIMI-3; Group 3, final angiogram was non-TIMI-3). Myocardial salvage index was calculated with area at risk using acute phase T2 high volume and chronic phase late gadolinium enhancement volume.

Results:
The age (Group 1 (n=31): median 70 y [interquartile range 43 -84] vs. Group 2 (n=23): 68 [35 - 81] vs. Group 3 (n=9): 72 [61 - 79], P = 0.386), prevalence of male (81% vs. 96% vs. 89%, P = 0.258), and door-to-balloon time (58 min [20 -218] vs. 65 [30 - 157], vs. 59 [25 - 111], P = 0.491) were similar between the groups. The relationship between salvage index and FSF was shown in figure1. The relationship between salvage index and myocardial blush grade was shown in figure 2. In the multivariate regressive analysis of the salvage index, chronic kidney disease (CKD), myocardial blush grade 3, door to balloon time and filter slow flow groups, CKD and myocardial blush grade 3 were found to be independently and significantly correlated.

Conclusions:
Non-myocardial blush grade 3, as a part of slow flow observed in the final angiogram, is associated with impaired myocardial salvage. However, temporal filter slow flow may not diminish myocardial salvage.
Abstract 4141280: Machine Learning Predicts 24-Hour Change in Decongestion Biomarkers in Hospitalized Heart Failure Patients
Authors: Harzand Arash , Vremenko Dmytro , Wilcox Alexander , Beskin Claire , Liao Ruizhi , Joseph Jacob
Published: November 2024

Background:
Despite recent advances, patients with heart failure (HF) often experience repeat hospitalizations and worsening clinical trajectories from inadequate decongestion. Evidence-based approaches for optimizing interventions in the acute hospital setting for patients with decompensated HF are needed. We evaluated whether machine learning (ML) models can accurately predict next-day levels for decongestion surrogates in hospitalized HF patients.

Hypothesis:
ML can accurately predict body weight, hematocrit, creatinine, and potassium values in the next 24 hours in hospitalized HF patients.

Methods:
We utilized national Veterans Affairs (VA) databases to study all patients admitted with HF from January 2014 to July 2022. Records including at least one value for at least one biomarker of interest (body weight, hematocrit, creatinine, and potassium) were included. Patients were randomly split into training (80%), validation (10%), and test (10%) datasets. We trained a recurrent neural network to predict each biomarker’s value on admission day n+1 using data until day n, simulating a scenario where a clinician monitors response to treatment (e.g., diuresis) over a 24-hour cycle. The model that performed best on the validation set was evaluated on the test set. The R
2
, mean absolute error (MAE), and feature importance were determined.

Results:
We identified 589,114 admissions involving 124,163 unique patients. The mean (SD) age on admission was 72 (10) years; 98% were male, 69% were white, and 25% were Black. The performance (R
2
, MAE) for each biomarker model was as follows: body weight (0.94, 6.15 lb.), creatinine (0.92, 0.21 mg/dL), hematocrit (0.86, 1.7%), and potassium (0.53, 0.27 mmol/L). The top predictive features across all models were intravenous or oral diuretic use, patient age, and diastolic blood pressure. The predicted 24-hour change in each biomarker based on total daily diuretic dose for five representative patients is demonstrated in the Figure.

Conclusions:
ML can accurately predict the 24-hour body weight, hematocrit, creatinine, and potassium values in hospitalized HF patients, suggesting the potential for AI to guide acute in-hospital management.
Abstract 4141285: Acute Hemodynamic Effects and Synthetic Cooling Agents in “Clear” E-cigarettes Marketed in Massachusetts After the Tobacco Product Flavoring Ban
Authors: Minetti Erika , Erythropel Hanno , Keith Rachel , Davis Danielle , Zimmerman Julie , Krishnan-Sarin Suchitra , Hamburg Naomi
Published: November 2024

Introduction:
Massachusetts (MA) enacted statewide regulation on all flavored tobacco products in June 2020. Thereafter, electronic cigarettes (e-cigarettes) labeled ‘clear’ emerged on the market. We studied the acute hemodynamic impact along with chemical analysis of ‘clear’ e-cigarettes of these novel products.

Methods:
In healthy young adults (age 18-45), we measured acute changes in blood pressure (BP) and heart rate (HR) following a 10-minute structured use of participants’ own e-cigarette, comparing ‘clear’ e-cigarette users with other flavored e-cigarette users and non-users. Chemical characterization and quantification of relevant flavorings and cooling agents (WS-3, WS-23) of 19 ‘clear’-labeled disposable e-cigarette liquids was carried out by gas chromatography/mass spectrometry.

Results:
Our data was collected between 04/2019-05/2023 and includes 22 ‘clear’ e-cig users, 115 non-‘clear’ flavored users and 73 non-users (Figure A). After the ban, participants that used ‘clear’ labeled e-cigarettes increased from 0% to 21%. Baseline BP and HR were similar across all groups. With acute use the increase in diastolic BP, mean arterial pressure, and HR was higher in ‘clear’ e-cigarettes users compared to both non-‘clear’ flavored e-cigarette users and non-users (Figure B). The greater increase in HR in ‘clear’ users remained when restricting non-‘clear’ users to Juul users (products that do not contain synthetic coolants) (8.9±7.4 vs 4.5±7.9, P=0.03).

All (19/19) ‘clear’ e-liquids were found to contain synthetic cooling agents WS-23 and/or WS-3, most (18/19) contain menthol, with selected products also containing other flavorants (Figure C).

Conclusion:
The presence of menthol and synthetic cooling agents alongside other flavorings in newly marketed ‘clear’ e-cigs is a direct violation of the MA flavored tobacco product regulation. Acute use of ‘clear’ e-cigarette led to greater hemodynamic effects compared to other flavored e-cigarettes and Juul, raising questions about the health effects of cooling agents. Monitoring novel products and their constituents to assess their health effects is needed to protect young adults.