bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4138942: Loss of the v-SNARE VAMP8 Protects Against Aortic Aneurysms: Implications of Impaired Platelet Cargo Release
Authors: Mohammadmoradi Shayan , Driehaus Elizabeth , Alfar Hammodah , Joshi Smita , Whiteheart Sidney
Published: November 2024

Introduction and Objective:
As vascular sentries, platelets, and their ability to release a host of bioactive molecules, are critical for vascular homeostasis as well as hemostasis. Despite data linking platelet activation to abdominal aortic aneurysms (AAA) and rupture, the underlying mechanisms remain poorly understood. This study addresses the hypothesis that VAMP8, the primary v-SNARE controlling platelet exocytosis, significantly contributes to AAA formation.

Approach and Results:
A retrospective, single-center, multiple comparisons study of adult aneurysmal patients admitted to UKHealthCare between 2004 and 2023 revealed a significantly lower platelet count in AAA patients than in healthy individuals. These results were also observed in experimental aneurysm models using an AngII-infused hypercholesterolemic mouse model, suggesting increased platelet consumption. Our results indicated a noticeable accumulation of platelets at elastin break sites and false lumen formation in the abdominal aortas of aneurysmal mice. The platelet accumulation showed significant colocalization with VAMP8, alongside a marked upregulation of VAMP8 in the thrombus segments of the aneurysmal tissue compared to the control. WT and VAMP8-/- mice were infused with AngII (1,000 ng/kg/min) or saline two weeks post PCSK9 AAV infection for 28 days using subcutaneously implanted Alzet mini-osmotic pumps. Our results revealed that VAMP8-/- mice are protected against AngII-driven aortic rupture. Both
in vivo
and
ex vivo
aortic diameter analysis indicated that VAMP8 deficiency profoundly attenuated AngII-induced AAA compared to controls. Bulk RNA-seq analysis on washed platelets isolated from VAMP8-/- compared to WT mice revealed distinct transcriptomic profiles with significant enrichment in pathways related to aortic remodeling and aneurysm pathogenesis. Further, RNA-seq analysis of suprarenal aortas (5-day AngII infusion) showed that VAMP8 deficiency significantly reduced extracellular matrix degradation and increased aortic wall stability, as observed by the downregulation of matrix metalloproteinases (MMPs) and the upregulation of collagen synthesis genes.

Conclusion:
VAMP8 deficiency results in the profound attenuation of aortic aneurysms, potentially via enhanced ECM stability, introducing a novel paradigm for understanding the impact of platelet cargo secretion in aortopathies.
Abstract 4138946: Psychological Stress and Risk of Heart Failure and Its Subtypes in the Women’s Health Initiative
Authors: Gathright Emily , Allison Matthew , Burg Matthew , Haring Bernhard , Liu Longjian , Liu Simin , Manson JoAnn , Martin Lisa , Saquib Abu Taiyab Nazmus , Shadyab Aladdin , Wassertheil-Smoller Sylvia , Weitlauf Julie , wells gretchen , Mouton Charles , Ockene Judith , Salmoirago-Blotcher Elena
Published: November 2024

Background:
Psychological stress affects cardiovascular (CV) health via multiple physiological and behavioral pathways. Few studies have assessed whether psychological stress impacts heart failure (HF) incidence. A prior large cohort study identified unique associations between perceived stress and HF subtype, but these associations were confounded by other health risk factors (e.g., prevalent baseline CV disease). No prospective study has evaluated these associations in women free of baseline CV disease.

Goal:
To evaluate the prospective association of psychological stress with incident HF and HF subtype risk in post-menopausal women.

Hypothesis:
Psychological stress is prospectively associated with an increased HF hospitalization risk, which may vary by HF type (HFpEF vs. HFrEF).

Method:
Of 29,703 post-menopausal women enrolled in the Women’s Health Initiative (WHI) free of baseline CV disease and pre-existing HF at first adjudication, psychological stress was assessed via an 11-item scale of stressful life events (SLE) over the past year (WHI screening, 1993-1998) and the 4-item Perceived Stress Scale (PSS; WHI Extension 2, 2010-2015). Incident HF was confirmed via adjudication of self-reported first hospitalization. Cox proportional hazards models adjusting for demographic, medical, and lifestyle factors were used to calculate hazard ratios associating stress quartiles with incident HF, HFpEF, and HFrEF hospitalization.

Results:
At screening, women were 62±7 years, 49% from underrepresented racial and ethnic populations, and 59% were at least high school graduates. At baseline women reported a mean of 2±.01 SLEs over the past year. Mean PSS scores were 4.16±3.09. Over a median of 15 years, there were 1,624 incident HF events (HFpEF, n=998; HFrEF, n=626). In fully adjusted models neither the number of SLEs or PSS scores were associated with HF risk(Table 1).

Conclusions:
In this WHI cohort, the number of SLEs and perceived stress were not prospectively associated with risk of HF, HFpEF, or HFrEF hospitalization. Future research is needed to understand whether specific types of stressors, stress measured more proximally to HF onset, or lab-based stress assessments may capture an association of stress with HF risk.
Abstract 4138955: Artificial intelligence-guided screening of rheumatic heart disease from single-view two-dimensional echocardiography
Authors: Oikonomou Evangelos , Nascimento Bruno , Pedroso Camargos Aline , Lombo Bernardo , McNamara Robert , Karnik Ruchika , Sable Craig , Ribeiro Antonio , Khera Rohan
Published: November 2024

Introduction:
Rheumatic heart disease (RHD) is the most common acquired heart disorder in children and adolescents worldwide. We developed and validated an automated artificial intelligence (AI)-guided RHD screening algorithm adapted for point-of-care ultrasonography (POCUS) in school-aged children.

Methods:
We employed a cross-domain transfer learning approach, in which a 3D convolutional neural network (CNN) was first trained to detect structural RHD deformation of the mitral or aortic valves in 244,523 videos, representing all views from 5,614 adult transthoracic echocardiograms (1:5 age and sex-matched cases and controls; median age 69 [58-80] years, 76.4% female) in a large US health system. The model was fine-tuned for stage ≥B (“definite”) RHD in 21,472 POCUS videos (2D parasternal and apical acquisitions) from 5,525 studies (75% training, 25% validation) in a pediatric screening program (median age 11 [IQR 10-13] years, 54.6% female) in Brazilian low-income schools. Testing was performed in a held-out set of 1,966 parasternal long-axis (PLAX) videos from 1,138 studies in Brazil (14 [1.2%] with stage ≥B RHD) as well as in an external pediatric screening set in Uganda consisting of 249 videos from 96 studies (34 [35.4%] with stage ≥B RHD) (
Fig. 1
).

Results:
Our model (
Fig. 2
) achieved a study-level AUROC (area under the receiver operating characteristic curve) of 0.88 across the held-out/external testing sets for identifying stage ≥B RHD from cardiac POCUS (
Fig. 3A
). On a video-level the model learned a continuous spectrum of phenotypes on PLAX acquisitions spanning stage ≥B (“definite”) and stage A (“borderline”) cases, ranging from a median video-level AI probability of 0.13 [0.01-0.73] for stage ≥B to 0.00 [0.00-0.01] for non-RHD POCUS (
Fig. 3B
). At the threshold that maximized Youden’s J in the held-out Brazil set, our algorithm’s performance in the set from Uganda showed 97% recall (sensitivity), a positive predictive value (precision) of 46%, and a negative predictive value of 95%.

Conclusions:
A transfer learning approach that employs multi-view learning achieves excellent performance for RHD on single-view two-dimensional cardiac POCUS without Doppler. Our study suggests a scalable approach to AI-enabled RHD detection with images that can be acquired by individuals with modest training.
Abstract 4138964: Longer AF Diagnosis-to-Ablation Time is Associated with AF Inducibility Post-Pulmonary Vein Isolation
Authors: Bailey Grace , Phalunas Caitlin , Lathia Minesh , Belden Elizabeth , Belden William , Thosani Amit , Silverstein Joshua , Shaw George , Cherian Tharian , Friehling Mati , Duan Chaojing , Liu Emerson
Published: November 2024

Background:
Post-ablation atrial fibrillation (AF) inducibility has been associated with AF recurrence and is often used as an endpoint for Pulmonary Vein Isolation (PVI). Little is known regarding factors affecting inducibility after PVI, as AF inducibility is common even after PV isolation. Prolonged episodes of untreated AF can result in remodeling of the atrium and the formation of new arrhythmogenic substrate, which may make treatment of AF more challenging. We hypothesized that longer diagnosis-to-ablation time (DAT) is associated with higher rates of post-PVI AF inducibility.

Objective:
To evaluate DATs in cases of inducible vs. non-inducible AF post ablation.

Methods:
A single-center, retrospective analysis of 168 consecutive patients who underwent 1
st
time PVI between 1/1/2022 and 12/01/2023 was performed. Following PVI, inducibility of AF was tested by programmed stimulation using decremental pacing in 50ms windows for 10 seconds each (from 400 ms down to 200 ms or until loss of 1:1 atrial capture). Results were categorized by type of rhythm induced (non-inducible, AF) and duration (sustained, non-sustained). DAT was obtained from review of the medical records. Descriptive statistics were used to compare demographics and AF type, and parametric and non-parametric tests were used for analysis of the diagnosis-to-ablation window and its relationship to inducibility.

Results:
There was no difference in demographic data or AF type between the two groups. 85 patients (50.6%), had no inducible AF. 83 out of 168 cases (49.4%) had inducible sustained AF. Overall DATs ranged from 0 to 40 years. DAT was significantly higher in the inducible vs. non-inducible groups (3.810 vs. 2.906 years, p=0.023).

Conclusion:
Longer DAT is associated with AF inducibility post-PVI despite successful ablation. This association may reflect the increased persistence of AF as it progresses over time. Future studies are needed to evaluate the clinical implications of DAT times.
Abstract 4139040: Prevalence and Clinical Characteristics of US Patients with Systemic Inflammation and Atherosclerotic Cardiovascular Disease With or Without Chronic Kidney Disease
Authors: Lv Lei , Liu Meixia , Strum Matt , Chastek Benjamin , Johnson Jonathan , Gluckman Ty
Published: November 2024

Background:
High-sensitivity C-reactive protein (hsCRP) is a well-established biomarker of inflammation. Systemic inflammation is a recognized risk factor for atherosclerotic cardiovascular disease (ASCVD); however, the prevalence of systemic inflammation (SI) and the associated patient characteristics remain unknown.

Aim:
To define the prevalence and clinical characteristics of patients with SI and ASCVD with or without chronic kidney disease (CKD).

Methods:
A retrospective cross-sectional analysis of US adults (aged ≥18 years) with any diagnoses of ASCVD evaluated with a hsCRP test using the Optum
®
de-identified electronic health record dataset between 2017 and 2021. SI was defined as an hsCRP level of 2–10 mg/L. The prevalence of SI was evaluated by calendar year, stratified to three groups by presence of ASCVD, ASCVD with any stage of CKD, and ASCVD with stage 3 or 4 CKD. Concomitant comorbidities and medications used were assessed and stratified by CKD severity.

Results:
Across the study period, prevalence of hsCRP testing among patients with ASCVD remained relatively stable (0.87–0.98%). Among patients who underwent hsCRP testing, SI was present in 38.0%, 42.3% and 51.5% of patients with ASCVD, ASCVD with CKD, and ASCVD with stage 3 or 4 CKD averaged across the study period, respectively (
Figure 1
). The prevalence of SI remained largely unchanged over the study period across the three groups (
Figure 1
). Among those with SI, a higher Charlson Comorbidity Index was noted in those with CKD: 0.75–0.78 in those with ASCVD, 0.99–1.21 in those with ASCVD and CKD, and 1.71–1.89 in those with ASCVD and stage 3 or 4 CKD. The most common medications utilized in those with SI were lipid-lowering therapy (70.5% [ASCVD], 72.7% [ASCVD with any CKD] and 75.4% [ASCVD with stage 3 or 4 CKD]) and antihypertensive therapy (72.8% [ASCVD], 79.3% [ASCVD with any CKD] and 86.7% [ASCVD with stage 3 or 4 CKD]) averaged across the study period.

Conclusion:
Among patients with ASCVD undergoing hsCRP testing, SI was common, particularly among those with stage 3 or 4 CKD. This finding may help identify at-risk individuals who are likely to benefit from treatment of SI.
Abstract 4139045: Suicide and Self-Harm with GLP-1 Receptor Agonists: A Meta-Analysis of Randomized Controlled Trials
Authors: Hosseini Kaveh , Ebrahimi Pouya , Batlle Juan , Maqsood Muhammad Haisum , Ayati Aryan , Long Clarine , McGowan Natalie , Tarabanis Constantine , Laynor Gregory , Heffron Sean
Published: November 2024

Background:
GLP-1 receptor agonists (RA) improve diabetes, reduce cardiovascular events, and cause substantial weight loss. However, concerns have been raised about increased adverse psychiatric effects – namely suicide. Given the explosive increase in use of these agents, detection of even rare side effects is of great clinical importance. We aimed to perform the first meta-analysis of adverse psychiatric outcomes (suicidal ideation/attempt/completion or self-harm) in randomized, placebo-controlled, clinical trials (RCTs) of GLP-1 RA.

Methods:
A comprehensive literature search through 8/29/23 was conducted to identify RCTs involving adults with diabetes and/or overweight/obesity treated with GLP-1 RA or placebo for ≥6 months. 7,229 non-duplicate articles were screened for inclusion and 144 had data extracted. After querying all available data sources, including direct contact with principal investigators or corresponding authors, 21 of the 144 studies were found to have recorded incidence of adverse psychiatric outcomes. A random-effects meta-analysis was performed to estimate risk ratios and 95% confidence intervals (CI) for the primary outcome.

Results:
In total, 36,168 subjects received GLP-1 RA and 30,445 placebo. The event rate was very low (63 – GLP-1 RA; 45 – placebo). The pooled odds ratio for incidence of the primary outcome was 0.88 [95% CI, 0.60-1.29]
Figure
. Notably, 6 studies, including a total of 11,828 subjects, had a history of suicide attempt/depression as exclusion criteria for enrollment. Removal of these studies did not change the overall findings (OR 0.77 [95% CI, 0.38, 1.57]).

Conclusion:
Our comprehensive meta-analysis of placebo-controlled RCTs does not support an association of GLP-1 RA use with increased adverse psychiatric events among adults with diabetes or overweight/obesity. However, these outcomes were recorded in <15% of all trials, and >1/5 excluded subjects predisposed to these outcomes. More research is necessary, and continued surveillance remains warranted, to establish the safety of GLP-1 RA, particularly in patients at risk for self-harm/suicide.
Abstract 4139067: Racial and Ethnic Variations in the Accuracy of International Classification of Diseases 10
th
Revision (ICD-10) Codes for Identifying Pulmonary Embolism
Authors: Bacare Bassil , Rashedi Sina , Krishnathasan Darsiya , Khairani Candrika , Bejjani Antoine , Lo Ying-Chih , Zarghami Mehrdad , Mahajan Shiwani , Caraballo Cesar , jimenez ceja jose victor , Jimenez David , Monreal Manuel , Secemsky Eric , Klok Erik , Hunsaker Andetta , Aghayev Ayaz , Muriel Alfonso , Hussain Mohamad , Appah-Sampong Abena , Aneja Sanjay , MOJIBIAN HAMID , Goldhaber Samuel , Wang Liqin , Zhou Li , Krumholz Harlan , Piazza Gregory , Bikdeli Behnood
Published: November 2024

Background:
International Classification of Diseases, 10th Revision (ICD-10) discharge diagnosis codes are commonly used to identify patients with pulmonary embolism (PE) for research, surveillance, or quality improvement. Ethno-racial disparities exist in the presentation, treatment strategies, and outcomes of PE, but it is unknown whether disparities extend to how PE is coded in electronic health records.

Methods:
The PE-EHR+ study was designed to validate ICD-10 codes for PE. We used data from Mass General Brigham (MGB). The reference standard was the manual chart review by two independent investigators using predefined criteria. Sensitivity and specificity for ICD-10 codes were determined by race and ethnicity.

Results:
1,712 randomly sampled patients in equal distribution with PE principal discharge codes, PE secondary discharge codes, and no discharge codes for PE were selected from MGB. The race and ethnicity of the patients were non-Hispanic White (n=1,368), non-Hispanic Black (n=160), non-Hispanic Asian (n=50), non-Hispanic other or unknown (n=84), and Hispanic or Latino (n=50). The sensitivity and specificity of ICD-10 discharge diagnosis codes for PE were similar across race and ethnicity (Table). The results for the principal discharge diagnosis codes showed low sensitivity (range: 45%-66.3%) but high specificity (range: 90.9%-96.7%) by race and ethnicity. The principal or secondary discharge diagnosis codes resulted in high sensitivity (range: 99.7%-100%) but low specificity (range: 66.2%-83.3%) by race and ethnicity. The hybrid approach encompassing principal codes or secondary codes plus diagnostic imaging codes displayed high sensitivity (range: 97%-100%) and moderately high specificity (range: 78.1%-90%) among different racial and ethnic groups.

Conclusion:
While the study shows the tradeoffs of various combinations of ICD-10 codes for identifying PE, reassuringly, there was no large variation by race and ethnicity.
Abstract 4139108: Identifying Predictors of Durable Treatment Response among Patients with Claudication; A Secondary Analysis of the CLEVER Trial
Authors: Hentati Firas , Secemsky Eric
Published: November 2024

Background:
Symptomatic peripheral artery disease (PAD) is prevalent and targeted therapies include optimal medical care (OMC), supervised exercise therapy (SET) and revascularization (ST). Although most PAD trials focus on objective outcomes, improvement in quality of life is important to the patient. The Supervised Exercise, Stent Revascularization, or Medical Therapy for Claudication (CLEVER) Trial examined longitudinal patient-reported outcomes to assess response to OMC, SET and ST. The predictors of symptomatic improvement have not been fully assessed.

Research Question:
What are the predictors of symptomatic response to therapy for patients with PAD?

Aims:
To assess how demographics, comorbidities, and treatment modality predict improvement in patient-reported outcomes as measured by the Peripheral Artery Questionnaire (PAQ).

Methods:
This is a secondary analysis of the CLEVER trial, which randomized patients with claudication to OMC alone, SET or ST. The primary outcome measure was PAQ at 18 months. Response was defined as a change in the PAQ Summary Score by the minimal clinically important difference (MCID) of ≥10 points compared with baseline. Multivariable logistic regression was used to identify predictors of response.

Results:
Of the 103 participants (66 male, median age 63 years) included in this analysis, 22 were randomized to OMC, 40 to SET, and 41 to ST. Sixty-five (63%) participants had a decrease in PAQ Summary score of 10 or more points at 6 months. Of 98 participants who completed the 18-month PAQ, 52 (55%) had a response to therapy. Compared to those randomized to OMC, on univariate analyses, participants randomized to SET had a 4.5 (95%CI:1.5-13.6) increased odds of response at 6 months and a 4.2 (95%CI:1.2-15.1) increased odds at 18 months. Those randomized ST had a 6.6 (95% CI:2.1-20.9) and 10.9 (95% CI:2.9-40.6) increased odds of response at 6 and 18 months respectively. When controlling for demographics, comorbidities, and ABI, SET (18-month OR 3.9; 95%CI:1.1-14.7) and ST (18-month OR11.5 95%CI 2.9-45.7) remained associated with symptomatic response at 6 and 18 months. Treatment group was the only independent predictor of clinically meaningful symptomatic improvement.

Conclusion:
Among randomized patients in the CLEVER trial, treatment with either SET or ST was most predictive of quality life improvement at 6 and 18 months. These interventions, with a prioritization of SET, should be more widely available and offered to symptomatic PAD patients.
Abstract 4139180: Navigating Trust and Preferences in Research Data Sharing: Addressing Racial Disparities for Inclusive Research Practices
Authors: Ninode Rivera Stephanie , Eslami Sarah , Zhao Yihong , Masterson Creber Ruth
Published: November 2024

Objective:
Contemporary data sharing policies from the National Institutes of Health have expanded data sharing. Participants' perspectives are not well understood and could have an adverse impact on participation in cardiac research. We evaluated participants' preferences for health data, and strategies to enhance trust in data sharing practices.

Methods:
In March 2023, we conducted a nationally representative online survey with 610 US adults. We implemented a cross-sectional survey that assessed: (1) participant preferences about health data they are willing to share with external entities (e.g. health policy institutions, public health organizations, health technology companies, private foundations, etc), and (2) the impact on trust in research if participants could decide which external recipients (e.g, clinical symptom, biological, mental health, sexual health) receive the data. We used logistic regression models to assess sociodemographic variances in their willingness to share different types of data.

Results:
Among 610 participants, the mean age was 46 years (± 16; range 19-93) of which 50% were female, 77% identified as White and 7% identified as Hispanic/Latinx. Figure 1 shows the adjusted odds ratio (ORs) and 95% confidence intervals (95% CI) for willingness to share different data types with public health institutions and health technology companies by self-reported race. Black participants were significantly less likely to share most health data with public health organizations, including mental health (biological (OR: 0.562 [95% CI 0.342, 0.920]), clinical symptom (OR:0.455 [95% CI 0.275, 0.756]), and imaging data (OR:0.488 [95% CI 0.258, 0.714]) compared to White participants. Fewer racial differences were noted for sharing different types of data with health technology companies. Moreover, 63% of participants expressed that their trust in researchers would improve if given control over the data recipients (Figure 2).

DISCUSSION:
Participants exhibit reluctance to share specific types of personal research data, emphasizing strong preferences regarding external data access. This highlights the need for a critical reassessment of current data sharing policies to align with participant concerns.

Conclusion:
It is imperative for data sharing policies to integrate diverse patient viewpoints to mitigate the risk of distrust and a potential unintended consequence of lower participation among racial and ethnic minority participants in cardiac research.
Abstract 4139226: Anticoagulation For Patients On Hemodialysis And Atrial Fibrillation
Authors: Ebrahimi Ramin , Alvarez Carlos , dennis paul
Published: November 2024

Background:
Anticoagulation is the standard treatment for the majority of patients with atrial fibrillation (AF) to reduce the risk of stroke. Anticoagulation is also utilized in patients with end-stage renal disease (ESRD) on hemodialysis (HD) who have AF. Such patients are at high risk for bleeding and stroke. However, limited data is available regarding utility of anticoagulation in such patients. The goal of this project was to assess the efficacy of anticoagulation to reduce the risk of stroke for patients with ESRD on HD who developed new onset AF.

Methods:
The national Veterans Affairs (VA) electronic health records were utilized to identify patients with ESRD on HD from 01/01/2000 to 01/01/2018. Those with AF prior to HD were excluded. In addition, those with stroke, mitral or aortic valve surgery prior to AF were excluded. Anticoagulants included warfarin, or apixaban, rivaroxaban, edoxaban and dabigatran, collectively termed DOACs. Patients were considered to be on an anticoagulation if they received anticoagulation for >1 month. All diagnoses were based on International Classification of Disease (ICD) 9
th
and 10
th
versions, and Current Procedural Terminology codes. Follow up period extended from the onset of AF to 01/01/2020 or death.

Results:
Over the study period 12,559,292 patients visited any of the VAs nationally. Of these, 89,081 were on HD without prior AF. Of those, 17,192 (19.3%) developed new AF. Of these 13,649 had no stroke, mitral or aortic surgery prior to the AF diagnosis. Of the 9,227 patients in the no anticoagulation cohort, 476 patient subsequently had stroke (5.16%). Of the 3,708 warfarin treated patients, 533 had subsequent stroke (14.37). Of the 358 DOAC patients, 34 (9.95%) had subsequent stroke. The difference in the stroke rates between those anticoagulated and those not anticoagulated was significant (P<0.01).

Conclusions:
These preliminary data reveal significant differences in the rate of stroke based on anticoagulation status, and potentially specific type of anticoagulation in HD patients with new onset AF. Further studies are indicated to assess both the safety and efficacy of anticoagulation in HD patients with new onset AF.
Abstract 4139260: Impact of Right Pulmonary Vein Anatomical Variations on Phrenic Nerve Trajectory in Pulmonary Vein Isolation
Authors: Rodriguez-Queralto Oriol , Wasiak Michal , Chaumont Corentin , Oraii Alireza , Lopez-Martinez Helena , Ferrari Victor , Hu Ray , Chery Godefroy , Stiffler Jeffrey , Marchlinski Francis
Published: November 2024

Background:
Anticipating phrenic nerve (PN) location relative to right pulmonary vein (PV) anatomy based on pre procedure imaging may limit the risk of PN damage.

Aims:
Analyze how the presence of a middle pulmonary vein (MPV) or its equivalent affects PN trajectory.

Methods:
The study included consecutive patients undergoing AF ablation from 2018 to 2022. PN location was mapped by high-output pacing. 3 zones were defined based on the most distal PN capture spot: Zone 1–no PN capture or capture only within right superior PV (RSPV) ostium, Zone 2-capture along the septal antrum of RSPV until mid-carina and Zone 3-capture extending the antral region of right inferior PV (RIPV) (Figure 1). Right PV anatomy based on MRI/CT was classified into typical anatomy (no MPV) versus MPV present or large proximal septal branch of RSPV near ostium (MPV equivalent). The presence of a MPV or equivalent and its association with PN trajectory and the need for antral/septal ablation line adjustments to avoid PN injury was analyzed.

Results:
Out of 103 patients included (median age 67y [IQR=12], 70% male; 73% paroxysmal AF). PN was mapped in zone 1 in 49% of patients, zone 2 in 21%, and zone 3 in 30%. PN capture in zone 3 was significantly higher in the presence of MPV (prevalence 59.1%, Prevalence ratio (PR)=16.6; CI95% 4-67.4) or MPV equivalent (64%, PR=17.9; CI95% 4.5-72.1) compared to no MPV group (3.6%). An ablation line modification more antral toward the septum was necessary in 28% of patients due to PN capture and was more common if MPV (50%, PR=7; CI95% 2.5-19.7) or MPV equivalent (56%, PR=7.8; CI95% 2.9-21.4) compared to no MPV (7%).

Conclusions:
A distal PN location into the RIPV's antral region is significantly more likely with a MPV or MPV equivalent. Adjusting the PV isolation line more septal is crucial if MPV is present. This finding is essential for planning transeptal puncture sites and catheter placement for effective and safe PV isolation during radiofrequency ablation.
Abstract 4139262: Combined Dilation of Rheumatic Mitral and Tricuspid Stenosis in Youngest Patient With Quadrivalvular Disease
Authors: Bharadwaj Prashant , Wasir Amanpreet , kalra ravi , Passwala Hemali
Published: November 2024

Background:
Rheumatic heart disease with involvement of all the four valves is extremely rare with anecdotal case reports. Severe symptomatic multivalvular involvement is also rare.

Case:
A 12-year-old boy presented with gradually progressive dyspnea over two years to current New York Heart Association (NYHA) class IV status. He was hospitalized for a week with fever, sore throat and migratory polyarthralgia three years ago. Examination- pallor, facial and pedal edema, malnutrition (height= 127 cm, weight= 27 kg, body-mass index= 16.8 kg/m
2
), Harrison’s sulcus, pulse= 90/minute, blood pressure= 104/64 mm of Hg, severe mitral and tricuspid stenosis, severe pulmonary arterial hypertension, and right ventricular failure. Electrocardiogram- sinus rhythm with right axis deviation and QRS morphology consistent with systemic pulmonary hypertension and severe mitral stenosis. X-Ray chest- bi-atrial enlargement with pulmonary arterial and venous hypertension. Echocardiography- severe mitral stenosis (mitral valve area= 0.3 cm
2
), trivial mitral regurgitation, Wilkins Score= 8/16, mean gradient= 16 mm of Hg (maximum= 40 mm of Hg), doming of the thickened tricuspid valve with severe tricuspid stenosis, thickened aortic valve leaflets with mild aortic stenosis and trivial aortic regurgitation, and doming of thickened pulmonary valve with a c notch and trivial pulmonary regurgitation. There was associated severe pulmonary hypertension (suprasystemic) with right ventricular systolic pressure of 140 mm of Hg.

Discussion:
In view of young age, malnutrition and a fulminant presentation of severe mitral and tricuspid stenosis, the management hinged around the percutaneous versus the surgical options. Key factors included young age, financial constraints, and repeated reluctance of parents for open heart surgery. The patient underwent a percutaneous dilation of mitral and tricuspid stenosis with an Inoue balloon in a single intervention.

Conclusion:
We describe quadrivalvular rheumatic heart disease with severe symptomatic mitral and tricuspid stenosis in the youngest ever reported case. The combined balloon dilation of both valves at this age is also not reported.
Abstract 4139265: APOL1 Kidney Disease Risk Variants Are Causal in Obesity
Authors: Kearney Andrew , YANG JOHNSON , Liu Esther , Kong Jiayi , Wright Matthew , Lin Jennie
Published: November 2024

Background:
Obesity-which develops from environmental and biological factors-is disproportionately more prevalent among individuals of African ancestry. Part of this difference may be due to DNA variants specific to African ancestry. Recent observational studies have reported an association between obesity and the common APOL1 G1 and G2 DNA variants, specific to individuals of sub-Saharan African ancestry. Compared to the G0 major allele, the G1 and G2 risk variants (RV) are known to increase the risk of kidney disease in African-ancestry patients and have been extensively studied in the renal context. However, no functional validation has established whether the APOL1 RV are also causal in obesity. The aim of this study is to address the hypothesis that APOL1 RV are causal in the pathogenesis of obesity independent of kidney disease.

Methods:
Because APOL1 expression is primate-specific, we leveraged transgenic G0 and APOL1-RV mice (n = 58), which were fed standard chow or high-fat diet (HFD) for 16 weeks. The mice underwent measurements of body mass, body composition by Echo-MRI, and tail cuff BP. Blood, urine, kidneys, perigonadal adipose tissue (AT), and bone-marrow derived macrophages (BMDMs) were examined for cardiometabolic traits.

Results:
Concordant with single-cell RNA-seq data of human AT (GSE176067) revealing APOL1 expression in multiple cell types, robust APOL1 protein expression was detected in AT of the APOL1 transgenic mice. Although no differences in body mass were seen among males, female APOL1-RV mice had higher body mass than G0 females in both the standard chow (p = 0.01) and HFD groups (p = 0.04). Both male and female mice on standard chow did not exhibit genotype-specific differences in body composition, but G0 female mice on HFD had significantly higher lean:fat mass ratio than female APOL1-RV mice (7.7 vs. 3.8, p = 0.04). In addition, female APOL1-RV mice on standard chow had significantly higher systolic BP than G0 females (129.5 vs. 107.6 mmHg, p = 0.04), while female APOL1-RV mice on HFD had more albuminuria than G0 females (43.4 vs. 22.7 mg/g, p = 0.01). Although qPCR assays of kidney and AT were unrevealing, APOL1-RV BMDMs modeling inflamed AT macrophages of obesity expressed significantly higher levels of Tnf than G0 when stimulated with interferon-γ.

Conclusion:
This is the first study to report a causal link between APOL1 kidney disease variants and obesity, seen more prominently in female transgenic mice.
Abstract 4139271: Investigation of familial hypercholesterolemia prevalence and association with cardiovascular disease in an African ancestry cohort.
Authors: Berry Alexander , Winters Alexandra , Kelly Melissa , Mohammed Nuha , Jones Laney , Gidding Samuel , Oetjens Matthew
Published: November 2024

Familial hypercholesterolemia (FH) is an inherited condition consisting of lifelong elevated LDL cholesterol levels and increased risk of cardiovascular disease. Among Western populations, the prevalence of FH has been reported to be between 1:212 to 1:331. African ancestry individuals are underrepresented in submissions to genetic resources used to determine variant pathogenicity and there are no known reports on the prevalence of FH in those populations. To create an African ancestry cohort, we performed principal component analyses on genetic data from Geisinger’s MyCode (N = 175,500) and the NIH’s All of Us (N = 98,590) cohorts to identify individuals who cluster with 1000 Genomes African superpopulation (1KG AFR). We assessed sequence variants in FH genes from our African ancestry cohort for pathogenicity using American College of Medical Genetics criteria. Lipid levels and use of lipid lowering medications were compared among those with and without a variant. Among 29,931 individuals who clustered with the 1KG AFR group, we identified 31 unique pathogenic or likely pathogenic FH variants among 108 individuals, yielding a prevalence of 1:277. Most of the pathogenic variants identified (94%) were missense variants in the
LDLR
gene. Mean age for individuals with a pathogenic FH variant was 40.5 years in MyCode and 50.4 years in All of Us. Of those with a pathogenic FH variant and at least one LDL measurement, we found that 52.5% had an LDL > 190mg/dl and 37.5% had an LDL > 250 mg/dl, compared to 5.7% and 0.6% of African ancestry individuals without an FH variant, respectively. The effect size of an FH variant on maximum LDL levels adjusted for age, sex, and principal components of ancestry was 90.4 mg/dL (95% CI, 69.8-111.0; p=1.1x10-17) in MyCode and 126.5 mg/dL (95% CI, 110.5-142.6, p=4.0x10-53) in All of Us. In the combined cohort, 29.6% of individuals with a pathogenic FH variant had been prescribed an LDL-lowering medication, compared to 20.9% of individuals without a variant. Overall, the prevalence of FH in an African ancestry cohort was consistent with the prevalence of FH in studies of European ancestry cohorts. The effect size of an FH variant on LDL in this cohort was large. These data suggest that African ancestry individuals with pathogenic FH variants have a high likelihood of increased LDL and concomitant cardiovascular disease risk and that there is an opportunity for additional identification and treatment of FH in this population.
Abstract 4139284: Most Important Predictors of 30-Day Death in Patients with Heart Failure Presenting with Acute Dyspnea
Authors: Kraevsky-Phillips Karina , Scott Paul , Thangavel Sarumathi , Al-Zaiti Salah
Published: November 2024

Background:
Heart failure (HF) manifests with burdensome symptoms leading to frequent emergency department (ED) visits and high rates of poor outcomes and mortality. Dyspnea is a nonspecific chief complaint, making risk stratification in this group very challenging. The purpose of this study was to determine patient characteristics related to poor outcomes in patients with HF seen in the ED for dyspnea.

Methods:
This was a secondary analysis of a retrospective observational cohort study of patients with known HF seen in the ED for a chief complaint of dyspnea between January 2018 and December 2022 at any one of 40 UPMC-affiliated hospitals in Pennsylvania. Trained independent chart reviewers collected study variables using a structured data collection form. Variables with <10% prevalence or >50% missingness were omitted. Multiple imputation was used to handle sparsely missing data. Primary outcome was all-cause death within 30-days of ED admission calculated from date of ED admission using death dates available in charts and manual obituary search. We used LASSO regression with 10-fold cross-validation to obtain the most significant predictors from 150 data points available early in the ED course (i.e., past medical history, initial vitals, demographics, ED treatments). Nine important variables were selected to build a logistic regression model to derive unbiased coefficients. Analysis was performed using Stata version 18.

Results:
The sample included 296 patients (mean age 73±14 years, 53% female, 13% Black, mean EF 50±13%) of whom 22 (7.4%) died within 30 days of ED admission. LASSO regression selected nine variables: age, systolic blood pressure, history of Afib/flutter, CAD, MI, stents, sleep apnea (OSA), fluid bolus in ED, and home aspirin. In the subsequent logistic regression using those variables, fluid bolus (OR=3.4, 95% CI 1.08-10.67, p=0.036) and history of sleep apnea (OR=0.09, 95% CI 0.011-0.76, p=0.027) remained significant.

Conclusions:
Our analysis suggest that patients who received a fluid bolus experienced higher odds of 30-day mortality and patients with a history of OSA experienced lower odds of mortality. The complex relationship of these variables with 30-day death should be investigated further.
Abstract 4139333: An Echocardiogram-Based Risk Model to Predict Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Sun Daokun , Chan Lap Sum , Norby Faye , Inciardi Riccardo , Soliman Elsayed , Alonso Alvaro , Solomon Scott , Shah Amil , Pan Wei , Chen Lin
Published: November 2024

Background:
Atrial fibrillation (AF) is often asymptomatic and detection of AF is challenging. 2D-Echocardiogram (2DE) provides a comprehensive assessment of cardiac structure and function, and hence, may be used to predict AF.

Aim: To derive a 2DE-based risk model to predict AF using supervised machine learning (ML).

Methods:
We included 5,445 older adults from the Atherosclerosis Risk in Communities (ARIC) study who underwent transthoracic 2DE at baseline (visit 5, 2011-2013) and had no known history of AF. Individuals were randomly allocated to the training and testing sets in a 7:3 ratio. Incident AF was ascertained from hospitalization records and death certificate during follow-up. Missing values of 2DE measures with <10% missingness were imputed 50 times via Multiple Imputation by Chained Equations (MICE), and those with ≥10% missingness were excluded from the analysis. The Lasso approach was used for variable selection based on the consensus of the 50 imputed datasets. Significant variables (P<0.05) were used to build a model for prediction of incident AF in the training set by Cox proportional hazards regression. Harrell’s C-index was used to assess model performance.

Results:
The median (IQR) age was 74 (71-79) years (59% female, 23% Black). During a median (IQR) follow-up of 7.0 (5.4-7.8) years, 738 participants developed AF. The cumulative incidence of AF was 1.4%, 5.0%, and 9.6% at 1, 3, 5 years, respectively. The table shows the hazard ratios for AF of each predictor in the final model. The Harrell’s C-index at 1-, 3-, and 5-year was 0.80, 0.72, and 0.73, respectively in the training set and was 0.76, 0.74, and 0.75, respectively in the testing set.

Conclusion:
Our ML derived 2DE-based risk model has good model discrimination for prediction of AF, setting the stage for a deep learning model using 2DE images for AF prediction.
Abstract 4139355: Improvement in Cardiorespiratory Fitness During Cardiac Rehabilitation: Effect of Smoking Status
Authors: Gaalema Diann , Savage Patrick , Khadanga Sherrie , Desarno Michael , Ades Philip
Published: November 2024

Background:
Patients who smoke have high-risk cardiovascular profiles. However, it is less well-known whether smoking interferes with gains made during cardiac rehabilitation (CR), such as improvements in cardiorespiratory fitness (VO
2peak
).

Hypothesis:
Current smoking impedes improvement in VO
2peak
during CR.

Aims:
To determine if smoking status was independently associated with improvement in directly measured VO
2peak
.

Methods:
Data were obtained from a prospectively collected clinical database at the University of Vermont Medical Center. Individuals were included if data was available on entry and exit VO
2peak
(measured during a symptom-limited treadmill test) and self-reported smoking status (current, former, or never). Data were extracted on sex, age, body mass index, comorbidity score (severity of exercise-limiting comorbidities) and number of CR sessions completed. Analyses of variance and linear regressions were used to test for associations between the aforementioned variables and change in VO
2peak
. Variables with significant associations were entered into multivariable general linear models predicting change in VO
2peak
.

Results:
2390 patients (111 current, 1114 former and 1165 never smokers) were included. Current smokers differed significantly from former/never smokers, being younger (58.3±10.8 vs. 65.4±10.2 and 64.2±11.2), having higher comorbidity scores (0.8±1.4 vs. 0.6±1.2 and 0.5±1.0), and attending fewer CR sessions (25.3±11.1 vs. 29.5±9.2 and 29.1±9.6). All variables examined were significantly associated with change in VO
2peak
except for number of CR sessions attended and remained significantly associated with change in VO
2peak
in the multivariable models. Estimated mean improvement (controlling for other variables) in VO
2peak
was [mean(SE)]: 1.6(0.3), 2.8(0.1), and 3.2(0.1) mLO
2
*kg-1*min-1 in current, former, and never smokers, respectively. Percent improvement in VO
2peak
also varied across groups [11.6(2.1), 16.8(0.7), and 18.2(0.7)%]. In both models, improvement in the current smoking group was significantly less than the other two groups (ps<.05 for all comparisons).

Conclusion:
Smoking status at CR entry was significantly, independently associated with improvement in VO
2peak
during CR.
Abstract 4139373: Cardiac Consequences of Acute Mania: A Case of Takotsubo Cardiomyopathy
Authors: ABDELSALAM MAHMOUD , Ahmed Maram , Ezaldin Shady , Gharib Elie
Published: November 2024

Introduction:
Takotsubo cardiomyopathy (TCM) is a transient condition characterized by left ventricular dysfunction, often triggered by stress, although its exact pathogenesis remains unclear. We are presenting a case of TCM triggered by an acute manic episode, shedding light on the interplay between psychological states and cardiac function. Additionally, this case underscores the heightened risk of QT prolongation and ventricular fibrillation associated with antipsychotic medications.

Case Description:
A 32-year-old female with a history of bipolar I disorder was admitted to the psychiatric unit for an acute manic episode and was immediately started on Olanzapine. On the second day of admission, the patient collapsed and was found to be in ventricular fibrillation. After three cycles of cardiopulmonary resuscitation and two direct current shocks, the patient achieved a return of spontaneous circulation and sinus rhythm. She was intubated and transferred to the ICU, where an EKG revealed a QTc of 497 ms (Figure.2). A follow-up EKG after 12 hours showed dynamic T-wave inversions and a prolonged QTc of 615 ms (Figure.1). Echocardiography indicated apical akinesis with severely decreased systolic function, with an ejection fraction of 30%. CT coronary angiography was normal. The patient was diagnosed with Takotsubo cardiomyopathy and started on metoprolol. On the fourth day of admission, an automatic implantable cardioverter-defibrillator was implanted. At six-month follow-up, the patient's EKG showed a normal QTc of 420 ms (Figure. 2), and echocardiography demonstrated an improved ejection fraction of 55%.

Conclusion:
This case supports the hypothesis of catecholamine-induced myocardial stunning as a primary mechanism of TCM, illustrated here in the context of acute mania. Physicians should consider TCM as a potential complication of acute mania. Screening EKGs in patients experiencing manic episodes could be beneficial. If abnormalities are detected, serial EKGs, echocardiography, and medication adjustments may help prevent this potentially fatal consequence of acute mania. Although Olanzapine is not strongly linked to QTc prolongation compared to some other atypical antipsychotics, diligent electrocardiographic monitoring and close observation for any QTc prolongation are crucial. These measures play a pivotal role in preventing potentially fatal consequences associated with cardiac arrhythmias.
Abstract 4139413: Free Testosterone is Associated with Lower Microvascular Function in Men with Prostate Cancer
Authors: Simon Abigayle , Looney Jacob , Blackburn Marsha , CRANDALL REVA , thomas jeffrey , Mullen McKay , Guha Avirup , Terris Martha , Klaassen Zachary , Weintraub Neal , Harris Ryan
Published: November 2024

BACKGROUND:
Cardiovascular disease (CVD) is the leading cause of death in men with prostate cancer (PC), and vascular function and arterial stiffness can predict CVD. High circulating free testosterone has been associated with increased arterial stiffness in PC, and higher circulating free testosterone early in prostate cancer diagnosis is associated with more aggressive disease. However, the role of circulating free testosterone and its influence on microvascular function in men with PC has yet to be elucidated. Thus, the present study sought to investigate the relationship between free testosterone and a comprehensive assessment of vascular health over time in men with PC.

METHODS:
Thirty-two men (Age: 67±1 years; BMI: 28.2±1.1 kg/m
2
) with PC participated in this study. Fasting blood samples were collected to assess both total and free testosterone. The flow-mediated dilation (FMD) test was used to assess conduit vessel function and microvascular function was assessed using local thermal heating (LTH). Arterial stiffness was assessed using augmentation index (AIx75). Blood samples and assessments of vascular health were conducted at baseline and every 3 months thereafter. Data are reported as mean±SEM.

RESULTS:
Free testosterone decreased (
p
=0.079) from baseline (5.0±0.5 pg/mL) to 3 months (4.6±1.1 pg/mL) and remained lower at 6 months (4.4±0.7 pg/mL), and 9 months (4.7±0.8 pg/mL). In addition, total testosterone was similar (
p
>0.05) from baseline (318±38 ng/dL) throughout the study. Free testosterone at baseline was inversely correlated with the change in LTH at 3 months (
r
=-0.601;
p
=0.030), 6 months (
r
=-0.638;
p
=0.035), and 9 months (
r
=-0.671;
p
=0.048). There was a positive correlation between free testosterone at baseline and the change in AIx75 from baseline to 3 months (
r
=0.668;
p
=0.013). No relationships between free testosterone and FMD over time were identified, nor were any relationships observed between total testosterone and indices of vascular health.

DISCUSSION:
Findings from this study demonstrate that a higher circulating free testosterone at baseline is associated with increased microvascular dysfunction and arterial stiffness over time. Future studies are needed to elucidate the precise mechanistic role of free testosterone on microvascular function in prostate cancer and whether therapeutic approaches can be used to mitigate the negative cardiovascular effects associated with lower concentrations of androgens.