bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4146020: Diverse Morphology and Proteomic Phenotypes of Calcification in Bioprosthetic Structural Valve Degeneration
Authors: Cahalane Rachel , Clift Cassandra , Blaser Mark , Turner Mandy , Kasai Taku , Campedelli Alesandra , Hendrickx Amber , Rega Filip , Billaud Marie , MUEHLSCHLEGEL JOCHEN , Aikawa Masanori , McNamara Laoise , Meuris Bart , Singh Sasha , Aikawa Elena
Published: November 2024

Introduction:
Fibrocalcific remodeling is an end-stage feature of bioprosthetic (BP) structural valve degeneration and calcific aortic valve (AV) disease. However, the processes governing BP calcification are understudied. Here we conduct a histopathological assessment of BP degeneration in the aortic position and build a proteomic comparison map of BP degeneration versus AV disease in humans.

Methods:
Macroscopic segmentation was performed on entire explanted degenerated bovine pericardial BP leaflets (n=48) and diseased AV valves (n=19) and validated with histology to classify their state (BP: non-degenerated/thrombotic/neotissue/calcified, AV: non-diseased/fibrotic/calcified). Segment-specific bulk mass spectrometry-based proteomics was performed on BP/AV tissues. Laser capture microdissection enabled spatially resolved proteomics of BP calcification within discrete bioprosthetic/thrombotic/neotissue matrices versus explanted non-calcified regions.

Results:
Principal component analysis revealed BP and AV proteomes (2,005 and 2,012 proteins) clustered according to their degenerated and diseased segments; BP thrombotic and BP calcified sample clusters overlapped (Fig.A). Correlations of segment proteome-wide abundances revealed the highest intra-tissue similarity between non-degenerated BP and calcified BP (r
p
=0.87). The highest inter-tissue similarity was found between BP neotissue and calcified AV (r
p
=0.69) (Fig.B). Histopathological observations supported these proteomic findings, confirming the presence of calcification within discrete BP matrices: bioprosthetic (22/59), thrombus (22/59), and neotissue (15/59) (Fig.C). Laser capture microdissection revealed that 252 proteins were enriched in either bioprosthetic, thrombotic, or neotissue matrix calcification compared to explanted non-calcified regions. Only 3% of differentially enriched proteins overlapped, suggesting different mechanisms (Fig.D).

Conclusions:
This is the first comparative proteomic study of segmented degenerated BP and diseased AV tissue. We identified 3 subtypes of BP calcification within bioprosthetic, thrombotic, or neotissue matrices. Spatial proteomics revealed different proteins associated with the calcification of these matrices.
Abstract 4146047: Improving Heart Failure Caregiver Competency Improves Caregiver Burden, Sleep and Mental Health
Authors: Higgins Melinda , Butts Brittany , Gary Rebecca , Dunbar Sandra
Published: November 2024

Introduction:
The COOL-HF (caregiver (CG) opportunities for optimizing lifestyles) randomized clinical trial tested a psychoeducational intervention (with and without exercise) to address heart failure (HF) CG risk for poor health outcomes due to the burden of caregiving. These analyses examine factors that affected response to the intervention.

Hypothesis:
HF CGs who received the intervention will have improved CG self-efficacy which will mediate improved outcomes (evidenced by lower depressive symptoms and CG burden and better mental health and sleep quality).

Methods:
CGs of persons with HF were randomized to 3 groups: usual care, psychoeducational only (PEd) or PEd plus exercise (PEdEx). The psychoeducational intervention included 4-weeks of in-person classes on nutrition, HF education, CG skills, communication, coping, self-care, and health improvement. In addition to sociodemographics, family caregiver version of Self-Care of Heart Failure Index (SCHFI) competency (self-efficacy) scale, Center for Epidemiological Studies-Depression (CES-D) score, Oberst Caregiving Burden Scale (time and difficulty scores), Pittsburgh Sleep Quality Index (PSQI) and Mental Health Continuum (MHC) were measured at baseline and 6m. The indirect mediation effect of the within-participant improvements in CG self-efficacy on outcomes were estimated with structural equation modeling using the lavaan R package to implement the MEMORE (Mediation and Moderation for Repeated Measures) algorithm.

Results:
The 127 CGs in the study were aged 55 +/- 11, 92% female, 58% Black, 55% spouses and 70% had a college or higher education. The HF patients’ severity ranged from NYHA class I (25%), II (25%), III (38%), to IV (12%). Significant mediation effects were found in both PEd and PEdEx groups for which SCHFI competence scores increased on average 1.99 +/- 3.15 points (moderate-to-large effect size (es) d=0.63) from baseline to 6m (p<.001), which mediated improvements in depression (indirect effect 95% confidence interval [-3.24, -0.22], small-to-moderate es=-0.18), Oberst time [-3.75, -0.27, es=-0.18], Oberst difficulty [-4.12, -0.64, es=-0.24], PSQI [-1.55, -0.14, es=-0.20] and MHC [0.37, 2.68, es=0.15].

Conclusions:
The COOL-HF psychoeducational intervention improved CG competency which mediated improvements in mental health, burden and sleep quality. These data suggest that effort to increase self-efficacy should be a key aspect of HF CG programs to promote improved psychosocial outcomes.
Abstract 4146077: Escalating burden of Ischemic Heart Disease and its trend attributable to Air Pollution in Southeast Asia, East Asia, and Oceania from 1990-2021: A Benchmarking analysis for the global burden of disease study 2021.
Authors: Dixit Aishwar , Katam Shruthi , Irfan Adan , shaikh salomi , dhillon nimrat , Syed Saif , Lakkimsetti Mohit , Shandilya Ashwinikumar , Adrejiya Parth , Bhalodia Paritaben , DESAI HARDIK , sharma kamal , AMIN VISHRANT
Published: November 2024

Introduction:
Ischemic Heart Disease (IHD) is the primary cause of morbidity and mortality across Southeast Asia, East Asia, and Oceania. Although there has been a lack of comprehensive studies on the burden of IHD attributable to air pollution, this study is the first to estimate its impact over the last three decades, including the initial two years of the COVID-19 pandemic.

Method:
Using global burden of disease tool, we estimated deaths, disability adjusted life years (DALYs), years lived with disability (YLDs), years of life lost (YLLs) due to IHD attributable to Air pollution by age, sex, year across the SEA, EA, and Oceania from 1990-2021.

Results:
From 1990 to 2021, the annual percentage change (APC) in total deaths due to ambient particulate matter pollution increased by 112% (95% UI: 79-151%), with DALYs rising by 77% (51-108%) and YLDs by 106% (91-120%). The age-standardized mortality rate (ASMR) increased by 124%, and DALYs rate by 102%. Timor-Leste observed the highest APC in ASMR at 329%, followed by China at 147%, while the highest DALYs rate was also in Timor-Leste at 321%, followed by the Solomon Islands at 141%. The highest number of deaths was recorded in the 80–84-year-old age group with 148,592, and DALYs were highest in the 70-74 age group at 2.2 million due to IHD attributable to AP in 2021. Males experienced a higher burden compared to females over the last three decades, with a total percentage change in deaths at 168% vs. 130%, YLDs at 128% vs. 153%, and YLLs at 112% vs. 73%.

Conclusion:
Urgent action is crucial to combat the escalating burden IHD due to AP in Southeast Asia, East Asia, and Oceania. Public stakeholders and policy makers must implement robust strategies to slash particulate matter pollution and protect public health.
Abstract 4146123: Exercise intolerance in HFpEF patients is related to skeletal muscle glycolytic ATP generation during exercise
Authors: Goldenberg Joseph , Samuel T , Lewsy Sabra , Schar Michael , Gerstenblith Gary , Weiss Robert
Published: November 2024

Introduction:
Exercise intolerance (EI) and early fatigue limit daily activities in patients with heart failure with preserved ejection fraction (HFpEF). Impaired skeletal muscle (SM) energy metabolism is associated with EI in HFpEF but the metabolic pathways that contribute to SM ATP production have not been studied. Given the importance of SM to whole-body glucose utilization, and the prevalence of insulin resistance and obesity in HFpEF, we examined glycolytic ATP production and its potential contribution to EI in HFpEF.

Hypothesis:
Previously unmeasured SM glycolysis limits ATP energy metabolism during exercise and is related to EI in HFpEF patients.

Methods:
We exploited non-invasive
31
P magnetic resonance spectroscopy to assess SM energy metabolism and glycolytic rates and their impact on EI in 62 HFpEF patients. Dynamic
31
P spectra of exercising calf muscle were acquired during graded plantar flexion exercise (PFE) until fatigue to measure high-energy phosphates, phosphocreatine (PCr) and ATP, and inorganic phosphate for determination of pH changes to quantify total glycolytic ATP during exercise.

Results:
Subjects were a mean age of 65 years, 53% were women, mean BMI of 39 kg/m2, 48% had diabetes and 48% were NYHA class III. Greater leg SM total glycolysis during exercise was closely associated with longer sustained exercise assessed by six-minute walk distance (Spearman r = 0.35; p=0.004), peak CPET VO
2
(Spearman r = 0.51; p<0.001), and PFE time to fatigue (Spearman r = 0.42; p<0.001). In contrast, mitochondrial oxidative ATP capacity was not related to exercise capacity. The rate of PCr decline was slower in those with longer six-minute walk (Pearson r = -0.42; p<0.001) and PFE (Spearman r = -0.95; p<0.001) durations and was closely related to greater glycolytic energy production (Spearman r = -0.3; p=0.017). This suggests that greater glycolytic ATP production during exercise in HFpEF patients is associated with slower SM high-energy phosphate decline and is itself closely associated with better physical performance inside and outside the MRI.

Conclusion:
Reduced SM glycolytic flux during exercise in HFpEF patients is associated with rapid SM high-energy phosphate decline during exercise and, importantly, closely tied to severe exercise intolerance in HFpEF measured by six-minute walk distance and peak CPET VO
2
. Impaired SM glycolytic capacity may offer a new metabolic target to treat HFpEF-associated disability.
Abstract 4146142: Constrictive Pericarditis Due to Sarcoidosis: Role of Multimodality Imaging in a Patient with a Metal Jacket Full of Calcification
Authors: Syed Alveena , El Hajjar Abdel Hadi , Abdulhai Farah , Saraswati Ushasi , Safdar Ahmad , Bhalla Jaideep Singh , Wang Tom Kai Ming , Ramchand Jay , Klein Allan , Motairek Issam
Published: November 2024

Clinical Presentation:
A 62-year-old male with a complex medical history, including pulmonary sarcoidosis, diabetes, constrictive pericarditis post partial pericardial stripping, cirrhosis, and congestive heart failure, presented with signs and symptoms of volume overload. Despite increasing diuretics and previous paracentesis, his condition continued to deteriorate. There were raising concerns for constrictive pericarditis due to cardiac sarcoidos. Echocardiography (TEE) showed pericardial thickening and calcification adjacent to the left ventricle and dilated IVC 2.4 cm (TTE). Cardiac magnetic resonance imaging (CMR) demonstrated conical deformity of the ventricles, thickened pericardium with signal void suggestive of calcification. Computed Tomography (CT) showed significant near circumferential pericardial calcifications. Subsequent catheterization confirmed constriction and identified a right coronary artery lesion. Following this, the patient underwent a redo pericardiectomy and coronary artery bypass grafting, at the Cleveland Clinic. However, his post-operative course was marked by complex challenges, including multi-organ dysfunction, the need for tracheostomy, feeding tube, renal replacement therapy, and recurrent ascites. Despite intensive care, his condition did not improve, leading to a transition to comfort care and eventually the patient passed away in December 2023.

Discussion:
This case highlights the intricate management of a patient with a myriad of underlying health issues. While multimodality imaging is pivotal in ensuring accurate preoperative diagnosis and guiding surgical interventions, it is important to acknowledge that challenges may persist in the postoperative phase. This case study underscores the vital role of multimodality imaging, irrespective of post-surgical outcomes, in facilitating precise diagnosis and delivering optimal patient care. The subsequent referral to the Cleveland Clinic for redo surgery, followed by a challenging and ultimately palliative care journey, shows the complexity of her clinical course and the importance of multimodality imaging and comprehensive care strategies.
Abstract 4146263: Radiation Induced Valvular Heart Disease complicated by Concomitant Radiation Induced Coronary Artery Disease
Authors: Basile Sean , Venkataraman Ramesh , Gallagher Robert
Published: November 2024

The cardiac adverse effects of radiation therapy include both radiation-induced valvular disease and radiation-induced coronary artery disease (RICAD). However, the management of each when present concurrently is minimally described by current research and guidelines.

A 60 year-old infectious disease physician with history of Stage IIA Hodgkin Disease s/p radiation therapy in 1976 (age 13) presented to cardiology for new dyspnea on exertion. She had known valvular heart disease followed with serial echocardiograms. Repeat TTE completed showing now moderate to severe aortic stenosis, moderate aortic regurgitation, moderate tricuspid regurgitation, and mild to moderate mitral regurgitation. After exercise stress testing aborted due to decrease in systolic blood pressure with exertion, patient underwent cardiac catheterization and found to have moderate-severe aortic stenosis as well as hemodynamically significant ostial disease of the right coronary artery and distal left main coronary artery; classic bi-ostial coronary stenosis characteristic of RICAD. After multidisciplinary discussion with interventional cardiology, cardiothoracic surgery, and second opinion with tertiary valve center, she was referred for surgical revascularization and aortic valve replacement (AVR). Patient underwent AVR with a 23mm bioprosthetic aortic tissue valve replacement, aortic root enlargement, tricuspid valve repair with 28mm ring, and three vessel coronary artery bypass grafting.

Notably, several retrospective studies have found increased mortality with surgical aortic valve replacement in patients with prior history of radiation with many centers preferring transcatheter aortic valve replacement as a safe and effective alternative in this demographic. Despite acknowledging this predilection, SAVR chosen in this patient specifically given her concurrent RICAD requiring revascularization. This case intimately highlights the need for further studies regarding management of radiation-induced valvular disease when complicated by RICAD.
Abstract 4146287: Social Determinants of Health: Impact on Mortality and Care Status for Adults with Congenital Heart Disease
Authors: Jackson Jamie , Mehta Rittal , Hardy Rose , Lopez Keila , Rudov Lindsey , Phillippi Ruth , Agarwal Anushree , ROEDER MARK , Saraf Sneha , Lewis Matthew , Saidi Arwa , Kanter Ronald , Sandhu Satinder , YOUNG THOMAS , Jacobsen Roni , Ruckdeschel Emily , Lubert Adam , Singh Harsimran , Zaidi Ali , Halpern Dan , Leezer Scott , Carton Thomas , John Anitha
Published: November 2024

Introduction:
Social determinants of health (SDOH) impact health outcomes for adults with congenital heart disease (CHD). We sought to understand how SDOH impacted access to care and mortality in adults with CHD.

Methods:
Electronic health records were queried across 13 PCORnet clinical sites to identify adults with CHD (CHI-RON study). Those with moderate or complex CHD lesion types were included in the current analyses. Social deprivation index (SDI), our predictor, was calculated using zip code scores (0-100) and were categorized into quintiles (from least to most deprived). Out of care status was defined as no cardiology visit for >2 years (complex CHD) or 3 years (moderate CHD) as of 2/28/20. Only centers with
>
90% positive predictive value on care status validation were included in the care status analysis. Mortality was confirmed through the National Death Index. Multivariable logistic regression assessed the association between SDI and outcomes (mortality, care status) with fixed effects for CHD complexity, age, sex, and random effects for sites.

Results:
Our cohort included 20495 patients with a median age of 33 years (range: 23-48), 50% with moderate CHD, 50% male, 10.3% non-Hispanic Black, 13.2% Hispanic, and 42% urban. Of 5916 included in the care status analysis, 41.7% were out of care. Higher (worse) SDI scores had greater odds of being out of care, with the greatest risk in the highly (OR 1.3, CI: 1.1-1.6, p< 0.001) and most deprived (OR 1.4, CI: 1.2-1.7, p<0.001) communities. SDI factors most associated with being out of care included regions with lower educational attainment (OR 1.6, CI: 1.4-1.8, p<0.001), lower vehicle (OR 1.5, CI 1.4-1.7, p<0.001) or home (OR 1.7, CI 1.5-2.0, p<0.001) ownership, and higher unemployment (OR 1.8, CI 1.5-2.2, p<0.001). Mortality rate was ~3% (n=618). Factors associated with higher odds of mortality included: living in highly deprived (OR 1.7, CI: 1.3-2.1, p<0.01) or most deprived (OR 1.6, CI: 1.2-2.1, p< 0.01) communities, Black (OR: 1.9; CI: 1.5-2.3, p<0.01) or Hispanic (OR: 1.6; CI: 1.2-2.1, p<0.01) race and ethnicity, and living in rural areas (OR: 2.0; CI 1.5-2.6, p<0.001).

Conclusions:
Adults with CHD living in areas with higher SDI scores may be at greater risk for not receiving recommended cardiology care and mortality; Black, Hispanic, and rural ACHD patients may be at higher risk for mortality. Further study is needed to understand how social and systemic drivers intersect with race to impact CHD.
Abstract 4146351: A Multicentre Study for Hands Only CPR (HOCPR) training assessment towards building a ‘Nation of Life Savers” in India
Authors: Ravikumar Thanjavur , Ravikumar Thanjavur , Sarkar Manuj , Debnath Dhrubajyoti , Behera Priyamadhaba , Ghate Dr Jayshri R , Trikha Divay , Samantaray A , Madhavi K , Sarma KVS
Published: November 2024

Failure to rescue a subject sustaining sudden cardiac arrest is a public health issue requiring urgent action. The awareness, knowledge&skills of HOCPR is very low and the need-gap is very high in India with world’s largest and diverse population (socioeconomic, cultural, linguistic&educational). We undertook a structured multicentred approach with the following elements for improving HOCPR awareness, education&training for generalisability and scalability: i) an IRB/IEC approved pre-post training survey; ii) train-the-trainer program iii) pilot study in one district of a state; iv) validation study in 5 states (data validation is available for 4 out of 5 sites as of now) located in disparate regions of India with part financial support through AHA grants in aid.

The pilot cohort of 46,012 trainees covered 27 of 32 revenue divisions (mandals) in one state, comprising students and community members of diverse sections of society. Pre- post training statistical analyses include McNemer’s test&ChiSquare.

Results:
The reason for non-readiness for HOCPR was” do not know how” in 92.9% of trainees in pre-test, and 98.6% reported that they learnt HOCPR in post -test(p<0.001). Pre- post education/ training comparison statistical analysis showed a significant improvement in knowledge (p<0.0001)&skill (p<0.0001). There was 82.8% improvement in knowledge, and 60.4% improvement in readiness; showing that ‘readiness’ requires more effort than knowledge/skills alone in HOCPR. The quality of training (Likert scale) showed 86% responding excellent/ very good; and the reasons for improvement being more training time and unevenness in quality of training in 14% of trainees.

The ongoing validation study cohort comprises 59,646 trainees. Pre-post survey corroborated the pilot data with regards to knowledge/skills of trainees and quality of training.

This prospective multicentre HOCPR training impact analysis provides scientific platform for scaling up in a most heterogeneous and vast population like India. Further studies are planned to improve HOCPR readiness as well as downstream analysis of sudden cardiac arrest victims receiving HOCPR at the scene for mitigation of death and enhanced quality of life of survivors transported to hospital.
Abstract 4146364: A refined definition for low-risk pulmonary arterial hypertension patients including mortality and morbidity
Authors: Fauvel Charles , Liu Yongqi , Correa-Jaque Priscilla , Everett Allen , Kanwar Manreet , Vanderpool Rebecca , Sahay Sandeep , Lin Shili , Benza Raymond
Published: November 2024

Background:
According to the European Guidelines, “low-risk” pulmonary arterial hypertension (PAH) patients is defined as a risk of death < 5% within a year and represents a treatment-goal. However, the impact of morbidity (e.g. hospitalization and clinical worsening), were not included in this definition.

Research Questions:
Can REVEAL 2.0 risk score further identify low-risk PAH patients for both morbidity and mortality?

Aims:
Using the REVEAL 2.0 risk score, to propose a modified definition of “low-risk” to include the risk of both morbidity and mortality at 1- and 3-years, respectively.

Methods:
A harmonized dataset from 8 PAH randomized controlled trials from the FDA was used for this analysis and REVEAL 2.0 risk score was calculated for each patient. Modified low-risk was a priori defined by “risk of death ≤ 5% at 3-years and risk of clinical worsening ≤10% at 1-year”. Clinical worsening was defined as any of the following: lung transplantation or hospitalization due to PAH worsening, initiation of prostanoids/chronic oxygen, 15% decrease in 6-MWD from baseline, a worsening of NYHA, addition of a new PAH medication.

Results:
A total of 4,122 PAH patients were included: median age 49 (36, 62) yo, mPAP 50 (40, 60) mmHg, PVR 10 (7, 14) WU, 6MWD 375 (306, 423) m, NTproBNP 884 (230, 3010) pg/mL. Patients with a REVEAL 2.0 risk score ≤ 4 had a 1-year clinical worsening free-survival and 3-year survival rate of 92% and 95% (
Figure 1
). The 3-years survival was significantly better in patients with a REVEAL 2.0 ≤ 4 compared to 5-6: HR=0.47, 95%CI[0.27-0.84], p=0.01. Compared to patients with REVEAL 2.0 risk score of 5-6 (“classical” low-risk), those with a REVEAL 2.0 risk score ≤ 4 (“refined low-risk”) had a better clinical, biological, hemodynamic presentation, and outcomes (
Table 1
).

Conclusion:
This study is the first embedding both morbidity and mortality within the definition of low risk for PAH patients and suggests that PAH patients with REVEAL 2.0 risk score ≤ 4 meet this definition. This definition may be a promising new treatment-goal strategy in future randomized controlled trials but also for daily clinical practice.
Abstract 4146374: Geographic polygenic heterogeneity of obesity across the United States
Authors: Truong Buu , Nakao Tetsushi , Koyama Satoshi , Bhattacharya Romit , Honigberg Michael , Hornsby Whitney , Natarajan Pradeep
Published: November 2024

Introduction:
The rising prevalence of obesity represents a public health crisis. Genetic analyses have established the strong heritable basis of body-mass index (BMI), which can be estimated by polygenic risk scores (PRS). However, the geographic distribution of the genetic risk of obesity is unknown.

Hypothesis:
BMI and BMI PRS vary across US regions and social indices interplay with BMI PRS.

Methods:
We use the nationwide All of Us Research Program to quantify BMI and BMI PRS heterogeneity in the European ancestry across US regions. Social indices include median income, vacant housing, deprivation index, having health insurance and poverty. PRS was computed using LDpred2 with 681275 individuals from GIANT consortium and UK Biobank. We compared heterogeneity within/between ZIP codes and states using linear mixed models. BMI and BMI PRS were adjusted with the first 100 principal components (PC) of ancestry. Our analyses were adjusted for age, sex and the first 10 PCs.

Results:
Across 93825 individuals, the mean (standard deviation,SD) age was 58.5(16.9) years, 56369(60%) were female, and the mean (SD) BMI was 29.2(7.2) kg/m
2
. BMI PRS explained 11.8%(95%CI 11.4-12.1%,P<2x10
-16
) of BMI variance. Pennsylvania had the highest significant variance explained (R
2
) by PRS with 13.2%(N=14288,P<2x10
-16
). BMI and BMI PRS were both spatially clustered (Moran’s I spatial autocorrelation=0.83 and 0.77, P<10
-16
,respectively). Urban areas had 0.12 SD-lower BMI compared to rural areas(P=4x10
-9
). Within each state, BMI and BMI PRS varied significantly, e.g. east Pennsylvania has a significantly lower BMI than the west. BMI variance explained by ZIP code was higher than by state (R
2
=2%,P=2x10
-37
vs R
2
=0.6%,P=7x10
-14
,respectively). High vacant housing and low median income were the strongest social indices associated with high BMI(P<2x10
-16
). Per 1-SD higher PRS,1-SD higher vacant housing and lower median income additionally increased BMI by 0.01 and 0.02 SD(interaction P<2x10
-16
),respectively. High poverty,no health insurance and low deprivation index are independently associated with low BMI.

Conclusion:
Understanding BMI differential distributions by genetic effects and social indices may uncover drivers of obesity across the US.
Abstract 4146376: Efficacy of Early Vs Delayed Catheter Ablation in Atrial Fibrillation: an Updated Meta-analysis
Authors: Singh Sahib , Tantry Udaya , Bliden Kevin , Ishaq Syed , Abuzahra Mohammed , Gurbel Paul , Kanjwal Mohammed , Lundgren Scott , Naksuk Niyada
Published: November 2024

Background:
Although observational studies have shown a higher rate of atrial arrhythmia recurrences in patients with atrial fibrillation (AF) undergoing delayed catheter ablation as compared with early ablation, a recent randomized controlled trial (RCT) did not show any such difference. We aimed to perform an updated meta-analysis of the available studies.

Methods:
Multiple online databases were searched for studies comparing early ablation (< 1 year) to delayed ablation (> 1 year) in patients diagnosed with AF. The outcome of interest was atrial arrhythmia recurrence at the longest follow up available. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effects model.

Results:
A total of 8 studies (1 RCT and 7 observational) with 5,171 patients (early ablation n=1,636, delayed ablation n=3,535) were included. Around 70% patients were men, mean age was 61 years and mean duration of follow up was 28 months. Patients with AF undergoing early catheter ablation had a lower rate of atrial arrhythmia recurrence when compared with the delayed ablation group (OR 0.57, 95% CI 0.44 to 0.73, p < 0.0001). Substantial level of heterogeneity was present between the studies (I2 = 67%).

Conclusion:
Performing catheter ablation early (within 1 year of diagnosis) in patients with AF may lead to significant reduction in atrial arrhythmia recurrence as compared with delayed ablation. The results of this meta-analysis, however, are subject to potential bias and heterogeneity.
Abstract 4146406: Association of Pulmonary Function with Right Ventricular Function and Longitudinal Change: The Echocardiographic Study of Latinos (ECHO-SOL) and Hispanic Community Health Study/ Study of Latinos (HCHS/SOL)
Authors: Duran Luciano Priscilla , Cedeno Serna Juan , Yuan Yawen , Zamora Cristian , April-Sanders Ayana , Kansal Mayank , Talavera Gregory , Shah Sanjiv , Daviglus Martha , Gonzalez Franklyn , Kaplan Robert , Hurwitz Barry , Rodriguez Carlos
Published: November 2024

Introduction:
Right ventricle (RV) changes secondary to severe lung disease are well described, but the association of pulmonary function tests (PFTs) and subclinical airflow obstruction with RV function is unexplored.

Methods:
Serial echocardiograms conducted 4.3 years apart on 1643 adults (mean age 56.4 years, 41.5% female) during ECHO-SOL visits 1 (2011-2014) and 2 (2015-2018) were analyzed. RV baseline function and change over time (from visit 1 to 2) were assessed by echocardiographic outcomes: RV fractional area change (RVFAC, %), tricuspid annular plane systolic excursion (TAPSE, mm), peak S’ velocity (cm/sec), tricuspid regurgitant maximum pressure gradient (TR max PG, mmHg), and RV velocity-time integral (RV VTI, cm). PFTs assessed by spirometry during HCHS/SOL visit 1 (2008-2011) included forced expiratory volume in 1 second (FEV1) in liters, forced vital capacity (FVC) in liters, and FEV1/FVC ratio. Regression models were utilized. All analyses were weighted to account for complex survey design.

Results:
Greater baseline FEV1 and FVC volumes were associated with more favorable RV systolic function at visits 1 and 2 evidenced by greater TAPSE, higher peak S’ velocity (only visit 1), and lower RV pulmonary flow (TR max PG, RV VTI). However, an inverse association was seen between FEV1 and RVFAC at visit 2. Greater baseline FEV1/FVC was also associated with higher peak S’ velocity at visit 1, lower TR max PG at visit 2 but less favorable TAPSE at visit 2. (
Table
)

Conclusion:
Better lung function was associated with healthier RV function at baseline and over time among Hispanic/Latino individuals, highlighting the association of pulmonary function with RV function.
Abstract 4146424: Evaluating

reported ethnicity

,

genetic ancestry

and three-way local-ancestry

admixture

with

preeclampsia

in GenPE,

a multi-center case-control study of Colombian women
Authors: Vaitinadin Nataraja Sarma , Gray Kathryn , Dupont Charles , Maher Matthew , SAXENA RICHA , Casas Juan , Colmenares Claudia , Serrano Norma , Giri Ayush
Published: November 2024

The role of genetic ancestry (GA) in hypertensive pregnancy disorders in Latin-American women is poorly understood.

Using data from a
multi-center case-control study (GenPE) of preeclampsia (PE) in young Colombian women
(median age = 19) of predominantly low socioeconomic status (2364 controls and 1811 cases), who identify as Afro-Caribbean (AFR-C), White Hispanic (HISP), Amerindian, and Mixed ethnicity,
we evaluated associations between 1) reported ethnicity, and 2) empirically estimated GA, with PE
. We performed 3-way admixture mapping using European (EUR), African (AFR) and Amerindian (AMR) ancestry references from the Human Genome Diversity Project using the FLARE software to estimate local and global ancestry in GenPE samples. Statistical significance threshold, for three-way local ancestry analyses, was empirically estimated using STEAM (P = 3.45x10
-6
).

In multivariable logistic regression models
for reported ethnicity,
AFR-C were 33% more likely to have PE (OR = 1.33; P = 0.02) than HISP women
.
In models evaluating empirically estimated global GA
,
AFR was positively associated (OR per 10% increase in ancestry = 1.05; P = 0.002)
, while AMR (OR = 0.91; P = 0.035) and EUR (OR = 0.95; P = 0.009) were inversely associated with PE. Additionally,
adjusting for reported ethnicity in models evaluating global GA and PE
changed estimates only marginally for AFR (OR = 1.04; P = 0.025) and EUR (OR = 0.92; P = 0.009).
Evaluation of GA and PE in a subset of women who reported AFR-C ethnicity
, showed stronger estimates for all global ancestries: AFR (OR = 1.11; P = 0.013, EUR (OR = 0.82; P = 0.026), and AMR (OR = 0.83; P = 0.01).
Association analyses with AFR local GA identified three loci associated with PE
.
The top locus
at chromosome 11, rs2021740 (a smooth muscle enhancer in
OTOG1
and near
MYOD1
), each additional allele of AFR origin associated with 27% increased odds of PE (OR = 1.27; P = 1.13x10
-7
).
The A-allele for this variant
is found in greater frequency in AFR reference populations (22%) than in EUR (5%).
Subgroup analyses with HELLP syndrome
(279 cases and 2364 controls) shows intriguingly opposite findings with increased risk for global AMR and EUR ancestry and decreased risk for AFR ancestry.

Using a genetically diverse hispanic population
, we show
genetic ancestry is associated with PE independent of reported ethnicity
and further demonstrate the
power of admixture mapping to identify a candidate locus for PE
.
Abstract 4146431: Acute Brain Attack: Peering Through The Esophageal Window In Cryptogenic Ischemic Stroke
Authors: Galeano Santiago , Adedinsewo Demilade , White Richard
Published: November 2024

The growing adoption of advanced imaging modalities, such as transesophageal echocardiography (TEE), has led to more frequent detection of cardiac structural abnormalities. While intracardiac cardiac tumors and shunts are infrequent and typically asymptomatic, their existence can precipitate severe outcomes, including stroke, myocardial infarction and sudden death.

Case Description:
A 69-year-old female presented with left sided facial droop, slurred speech and left arm weakness. A computed tomography angiography revealed focal occlusion of the distal right middle cerebral artery. She was initiated on thrombolytic therapy and experienced resolution of symptoms. Transthoracic echocardiogram revealed right to left shunting consistent with a patent foramen ovale (PFO). Further workup with TEE confirmed the presence of a PFO but also detected a mobile echogenic mass on the aortic valve leaflet, indicative of papillary fibroelastoma (PFE). Cerebral infarction was attributed to an embolic event, with the PFO and PFE being likely culprits.

Discussion:
Current guidelines give a conditional recommendation, low certainty of evidence, for PFO closure in adults older than 60 years, although some observational studies have shown some risk reduction in older patients. The key trials showing clinical benefit of PFO closure were in adults younger than the age of 60. For left sided cardiac tumors, such as PFE, guidelines give a 2A recommendation for resection. Addressing the risk for recurrent stroke in this 69-year-old patient was an essential part of stroke care, as such, a multi-disciplinary team of experts including cardiology, neurology, and cardiothoracic surgery was conveyed. The decision was to proceed with surgical intervention in addition to antiplatelet therapy to achieve optimal risk reduction. The patient subsequently underwent successful surgical removal of the PFE with native valve preservation and PFO closure.

Conclusion:
Cardiac PFEs and PFOs can be associated with increased stroke risk. Employing appropriate imaging techniques and timely interventions are of utmost importance in stroke management.
Abstract 4146481: Association of Atrial Fibrillation with Lamotrigine in Bipolar I Disorder: An Observational Cohort Study
Authors: Kim Sodam , Welch Landon , De Los Santos Bertha , Radwanski Przemyslaw , KIM KIBUM , Munger Mark
Published: November 2024

Objective:
Atrial fibrillation (AF) is the most common arrhythmia with the incidence and prevalence increasing worldwide. Lamotrigine (L) is a widely prescribed medication for Bipolar I disorder (BPI). L reduces intracellular sodium through inhibition of the voltage-gated sodium channels which slows cardiac conduction velocity. The mechanism can lead to an onset of AF. The aim of this study was to examine the incidence of AF in L patients without a history of cardiac arrhythmias or structural heart disease (SHD) vs controls prescribed common medications for BPI.

Methods:
We identified adult patients with BPI who received L or control agents (C) including lithium, quetiapine, valproate, and risperidone from Merative MarketScan
®
Commercial Claims and Medicare Supplemental Database. Patients were naive from AF at least six months prior to receiving L or C. Onset of AF was determined using ICD 9 and 10 codes. Patients were censored for generating the Kaplan-Meier cumulative incidence if switched between L and C, discontinued L or C during follow-up, end of continuous enrollment or end of one-year follow up. Onset of AF on L versus C was compared using hazard ratio (HR) calculated from a multivariable Cox-proportional hazard regression model. As a sensitivity analysis, we performed an analysis using a propensity score matched cohort.

Results:
The BPI cohort consisted of 150,470 L vs. 204,704 C patients with 145,467 pairs for PSM. The 1-year cumulative incidence of AF from L and C was 0.764% and 0.642%, respectively, calculating a HR of 1.257 [95% CI: 1.0878-1.4534],
p
=0.0019. (Figure 1). The number of patients needed for one AF incidence/year is 820. Results from the sensitivity analysis were very similar.

Conclusions:
In adult naïve AF patients, L compared to C taking commonly prescribed BPI medications was associated with a higher risk of AF.
Abstract 4146486: Prevalence, Incidence, and Progression of Cardiovascular-Kidney-Metabolic Syndrome in a Diverse Nationwide Cohort
Authors: Tan Savannah Xinyi , Li Fan , Mac Grory Brian , Lusk Jay
Published: November 2024

Introduction:
Recent studies using cross-sectional survey data have suggested high prevalence of cardiovascular-metabolic-kidney syndrome in the United States. However, these studies are limited by their cross-sectional design and cannot estimate progression or incidence reliably. In this study, we use the longitudinal nature of the AllofUs cohort to estimate the incidence and observe the progression and impact of CKM syndrome stages within a diverse cohort.

Research Aims:
To understand the distribution and impact of various stages of CKM syndrome within a diverse population cohort over an extended period and identify risk factors for CKM progression.

Methods/Approach:
Utilizing data from the AllofUs Research platform, we conducted a longitudinal analysis of patients within the cohort. Prevalence was calculated annually, while incidence was estimated by identifying new diagnoses of CKM syndrome. The incidence rate was calculated as the number of new diagnoses over the number of people at risk of developing that stage, using a one-year look-back window. We defined CKM stages according to recent AHA criteria, and additionally created three additional stages, which we termed Stage 5 (CVD and CKD stage 3-5), Stage 6 (>=2 CVD and CKD stage 3-5), and Stage 7 CKM (>=2 CVD, CKD stage 3-5, and >= one metabolic risk factor).

Results:
Our analysis revealed that the prevalence of CKM syndrome increased over the study period. For instance, the prevalence of Stage 1 CKM syndrome increased from 64.7% in 2018 to 80.18% in 2021, while Stage 2 CKM syndrome rose from 84.5% in 2018 to 92.91% in 2021. The incidence of various CKM stages in 2021 are shown in Table 1. The prevalence of all CKM stages are shown in Figure 1. At the conference, we will present models of risk factors for progression of CKM over time.

Conclusions:
More than 9 in 10 participants in a large nationwide cohort had Stage 2 CKM and the annual incidence of CKM ranged from 12% for Stage 1 CKM to ~3% for stage 4 CKM.
Abstract 4146529: Impact of Connective Tissue Features on Vascular Outcomes in Fibromuscular Dysplasia
Authors: Ravi Srekar , Bcharah George , Firth Christine , Saugstad Austin , Osundiji Mayowa , Wang Yuxiang , Ayoub Chadi , Shamoun Fadi
Published: November 2024

Introduction/Background:
Fibromuscular Dysplasia (FMD) is a non-atherosclerotic vascular disease that primarily affects medium-sized arteries and is characterized by abnormal cell development in the artery walls. Recent studies have suggested that various connective tissue features may be prevalent in patients with FMD, however the clinical significance of these findings on the disease course are uncertain.

Research Questions/Hypothesis:
We hypothesized that the presence of connective tissue features in patients with FMD might indicate a more severe disease course, potentially associated with increased severity of vascular complications.

Goals/Aims:
To evaluate the association between connective tissue features and the severity of vascular complications in FMD patients on outcomes including dissections and stroke.

Methods/Approach:
This cross-sectional study involved 2,454 patients diagnosed with FMD at a tertiary referral center. Patients were classified into two groups based on the presence (n=324) or absence (n=2130) of connective tissue features (pectus deformity of any kind, scoliosis, pneumothorax, inguinal hernia, uterine rupture, bowel perforation, Achilles tendon rupture). We evaluated the incidence of dissections and ischemic or hemorrhagic strokes using odds ratios and chi-squared tests.

Results/Data:
The cohort consisted of 2,454 participants with an average age of 64.8 years, of whom 89.1% were female and 92.4% identified as White. When comparing groups with and without connective tissue features, there were no significant differences in the prevalence of aneurysms at any site. Among the subgroup of FMD patients with connective tissue features (n=234), prevalent conditions included pectus (12.35%), scoliosis (47.22%), pneumothorax (16.67%), inguinal hernia (13.58%), uterine rupture (16.36%), bowel perforation (6.48%), and Achilles tendon rupture (1.85%). Vascular outcome analysis showed significant differences: the odds of experiencing a stroke were higher in patients with these features (odds ratio: 1.60; P-value: <0.01), whereas the odds of experiencing dissections were lower (odds ratio: 0.77; P-value: 0.03).

Conclusion:
The presence of connective tissue features in patients with FMD is associated with 60% higher odds of experiencing a stroke, equivalent to a 1.6-fold increase, compared to those without these features. This association may represent a novel finding in the literature, warranting further investigation.
Abstract 4146542: Effect of Beta-Blockers on Mortality in Patients with Tachycardia in the Setting of Sepsis and Septic Shock: A Meta-Analysis of Randomized Controlled Trials
Authors: Chilingarashvili Giorgi , Ahluwalia Vibhor , Mondal Avilash , Ahluwalia Vaibhav , Siddique Muhammad Saad , Chung Duy , Jaiswal Jay , Ha Quang Dat , DSilva Reeve , Samudrala Gayathri , Truong Vien
Published: November 2024

Background:
Beta blockers have the potential to mitigate the damage caused by adrenergic overdrive in septic shock. However, there is limited data supporting their effectiveness in controlling heart rate in these patients. Recent meta-analyses have demonstrated that beta-blockers can lower mortality rates in patients with sepsis. To evaluate the efficacy of beta-blockers in sepsis and septic shock, we conducted a comprehensive systematic review and meta-analysis.

Methods:
We performed a systematic review and meta-analysis by thoroughly searching MEDLINE, Scopus, and the Cochrane Database of Systematic Reviews to evaluate the efficacy of beta-blockers in sepsis and septic shock. Random-effects models were utilized to pool effect sizes. The DerSimonian-Laird estimator calculated between-study variance, and the Jackson method was employed to determine a 95% confidence interval (CI).

Results:
Our analysis included 8 eligible studies with a total of 893 patients (446 in the beta-blocker group, with 64% being female, and 447 in the placebo group, with 59% being female) at 28 days of follow-up. In the beta-blocker cohort, there were 171 deaths (38.3%), whereas the control group had 212 deaths (47.4%) at 28 days of follow-up. The use of beta-blockers did not significantly improve overall 28-day mortality (pooled odds ratio, 0.59; 95% CI, 0.34-1.03; p = 0.07) (Figure).

Conclusion:
The findings of this systematic review and meta-analysis suggest that beta-blockers do not significantly enhance survival rates among patients with sepsis and septic shock.
Abstract 4146553: Efficacy and Safety of Catheter Ablation in Patients with Hematologic Malignancies
Authors: Paranjpe Ishan , Rangan Ekanath , Narayan Sanjiv , Baykaner Tina , Fazal Muhammad
Published: November 2024

Introduction:
Patients with cancer have an increased risk for arrhythmias. Patients with hematologic malignancies face unique challenges in medical management of arrhythmias including increased bleeding risk limiting the use of anticoagulation therapies, increased clotting risk due to malignancy leading to a higher risk of stroke in the setting of atrial arrhythmias and lastly drug-drug interactions with chemotherapy agents limiting medical treatment options of arrhythmias. Safety and efficacy of catheter ablation in patients with hematologic malignancies have not previously been assessed.

Hypothesis:
We hypothesized that catheter ablation in patients with hematologic malignancies is safe, with reasonable acute and long term outcomes.

Methods:
We performed a retrospective analysis of consecutive patients with hematologic malignancies who underwent catheter ablation of AF, documenting procedural safety, acute and long term outcomes.

Results:
We identified 33 patients (n=21 with chronic lymphocytic leukemia, n=3 with chronic myeloid leukemia, n=4 with Waldenstrom's Macroglobulinemia, n=5 other) who underwent catheter ablation for arrhythmias after oncologic diagnosis between 2013-2024. Mean left-ventricular systolic ejection fraction was 57 ± 10%. Mean indexed left-atrial volume was 43±17 ml/m2. 11 (33%) patients underwent AF ablation alone, and 12 (36%) patients underwent AF and AFL ablation. 7 (21%) patients underwent typical AFL ablation with a cavotricuspid isthmus ablation alone. 5 (15%) patients underwent other SVT ablations (AVNRT, AT). 1 (3%) patient had pericardial effusion requiring pericardiocentesis. Over a mean follow up of 26 ± 22 months from catheter ablation, 12 (36%) patients had their oncologic therapy held due to arrhythmias. Out of the 23 patients that underwent AF ablation, 10 (43%) had AF recurrence at 2-year follow up. Of the patients who had AFL ablation, 2 (11%) had recurrent AFL at 2 year follow up. No recurrences were noted in the SVT ablation group. 17 (51%) patients were treated with tyrosine kinase inhibitors (TKI) which have been associated with incident AF, and 13 (39%) were maintained on TKIs at the time of ablation.

Conclusion:
Catheter ablation can be a safe and effective strategy for management of arrhythmias in patients with hematologic malignancies, with outcomes similar to the general population.