tbuckley/cabot-search huggingface dataset:
Abstract 4143909: Ectopic Fat Distribution and Adverse Muscle Composition in South Asians: Findings from the UK Biobank
Authors: Sanaa Tejani, Jennifer Linge, Ian Neeland, Anand Rohatgi, Jason Gill, Olof Leinhard, Naveed Sattar
Journal: Circulation (2024)

Background: South Asians (SAs) have higher risk of diabetes and cardiovascular disease compared with other ethnicities; however, detailed analyses of their body composition profile (BCP), including ectopic fat, muscle mass and muscle quality are lacking. Such data may help explain the higher rate of type 2 diabetes (T2D) in SAs, as muscle mass and quality are increasingly recognized as being linked to long-term health outcomes. Aims: This study utilizes imaging data from the UK Biobank cohort to compare body composition between SAs and white Europeans (EUR) to better understand ethnic differences in fat distribution and muscle composition. Hypothesis: We predict that SAs will have higher levels of ectopic fat (visceral-, liver-, and muscle fat) than matched EUR, which may explain their higher rates of T2D. Methods: Using UK Biobank imaging data captured by MRI, we compared body composition data in SAs (n=323) without T2D relative to age, sex, height and weight-matched EUR (matched 5:1 to SA group). We also compared BCP in 66 SAs with T2D versus matched EUR (matched 3:1 to SA group). Results: SAs without T2D had higher overall levels of body fat compared to EUR (mean difference in: visceral adipose tissue 0.20 L; abdominal subcutaneous adipose tissue 0.93 L; liver fat 0.92 percentage points (pp); muscle fat infiltration (MFI) 0.59 pp, all p&lt;/=0.001) and lower muscle volume (mean difference -0.61 L, p&lt;0.001) (p-values adjusted for sex, age, and BMI). Adverse muscle composition (MFI &gt;75 th percentile and muscle volume &lt;25 th percentile) was more prevalent in SAs (19.9% vs 7.9%, p&lt;0.001). Differences remained significant after further adjustment for prevalent disease, lifestyle and socioeconomic factors. SAs with T2D had similar BCP compared with matched EUR with T2D. Conclusions: SAs without T2D have greater visceral, liver, and muscle fat accumulation, and lower muscle volume compared to EUR. These findings may underlie their greater risk for T2D and atherothrombotic outcomes, especially as BCP was similar when comparing SAs with T2D to matched EUR with T2D. Lifestyle modification to increase physical activity and reduce weight gain may offset cardiometabolic risks in SAs through favorable changes in body composition.
Abstract 4143994: Unraveling the Genetic Overlaps in Heart Failure Subtypes: A Systems Biology Approach
Authors: Mirko Vierislav Pavicic Venegas, Kyle Sullivan, Jay Gopal, Hendrika Vlot, Matthew Lane, Maryam Rahafrooz, Danne Elbers, David Gagnon, Qin Hui, Chang Liu, Yan Sun, Jacob Joseph, Daniel Jacobson
Journal: Circulation (2024)

Background: Heart failure (HF), a progressive condition with a complex etiopathology causes significant morbidity, mortality, and reduced quality of life. HF affects 64 million people worldwide and imposes a global healthcare burden exceeding $346 billion annually. Currently, HF is classified into two major clinical subtypes based on cardiac contractility: HF with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). Given the complex pathophysiology of HF, we utilized systems biology tools applied to gene-level results from genome-wide association studies (GWAS) of HF, HFrEF, and HFpEF to identify underlying molecular pathways underlying these phenotypes. Methods: We utilized the union of three SNP-to-gene mapping methods: SNP-nearest gene, MAGMA, and H-MAGMA which uses Hi-C datasets from cardiovascular, lung, and liver tissues. Additionally, we built a gene-gene multiplex network from protein-protein interactions, transcription factor-target relationships, and predictive expression networks created with explainable-Artificial Intelligence (AI) algorithms from cardiac/metabolic layers, aorta, atrial appendage, left ventricle, coronary artery, whole blood plus lymphocytes, lung, and liver. The multiplex network was then used by the systems biology tools Gene set Refinement through Interacting Networks (GRIN) to refine the genes assigned from SNPs, while Multiplex Embedding of Networks For Team-Based Omics Research (MENTOR) grouped genes into functional clusters using hierarchical clustering of network embeddings. Results: Multiple SNP-to-gene assignment methods identified 51 genes for HF, 6 for HFpEF, and 109 for HFrEF. GRIN retained 42 connected genes for HF, 4 genes for HFpEF, and 78 genes for HFrEF. Ultimately, 119 unique genes were identified in total, with 86 of them being retained by GRIN. MENTOR clustering identified key biological processes affected by these genes including cytoskeletal function, extracellular matrix composition, inflammatory cytokine activity, and post-transcriptional modification of mRNA. Conclusion: Utilizing systems biology approaches, we were able to identify biologically connected genes and distinct molecular pathways underlying HF, HFrEF, and HFpEF.
Abstract 4143893: Combining Noncoding and Coding Genetic Variation Improves Arrhythmia Risk Prediction
Authors: Tanner Monroe, Lorenzo pesce, Samuel Kearns, Patrick Page, Lisa Dellefave-Castillo, Gregory Webster, Megan Puckelwartz, Elizabeth McNally
Journal: Circulation (2024)

Background: Ventricular arrythmias are highly heritable disorders and can cause sudden cardiac death (SCD). However, clinical genetic testing identifies pathogenic variants in less than 20% of nonischemic SCD cases. Additionally, there is considerable overlap in cardiomyopathy and arrhythmia (CMAR) genetics. Identifying genetic risk is important for predicting who might benefit from clinical intervention. We hypothesized that combining common, regulatory, and coding genetic variation could improve genetic risk prediction. Methods: We established a cohort of 1042 individuals with nonischemic arrhythmia risk (n=505, mean age 37) or controls, lacking cardiac or arrhythmia related diagnostic codes (n=537, mean age 58). Genome sequencing was analyzed for rare variants in CMAR and epilepsy genes, and extended to include noncoding variants in the regulatory regions of these genes. We also included common variants derived from polygenic scores for 18 cardiac rhythm and myopathic disorders. We then created a risk stratification algorithm that incorporated all 3 analyses. Results: When comparing the top quintile to the lowest quintile of scores, the 18 polygenic scores had an odds ratio of 5.0 [95%CI 3.8-6.7], indicating significant contribution from common variation. Coding region analysis demonstrated an enrichment of ultrarare and pathogenic CMAR and epilepsy gene variants in the arrhythmia cases compared to controls. The high risk arrhythmia cases also had a &gt;1.5-fold enrichment of ultrarare regulatory variants mapping to CMAR/epilepsy genes. As a predictor, the combination of common, coding, and regulatory variant analysis performed best, with the top 20% of the cumulative risk score carrying an odds ratio of 18.4 [95%CI 12.7-26.9], outperforming any subset of variant classes. A replication cohort confirmed these results. Importantly, this risk analysis performed well in individuals without monogenic arrhythmia risk (genotype negative cases). Conclusions: A comprehensive genetic risk score that includes noncoding and polygenic analyses can improve arrhythmia risk stratification.
Abstract 4143839: Irregular Sleep Duration is Associated with Altered 24-Hour Heart Rate Profile in Patients Enrolled in Cardiac Rehabilitation
Authors: Naima Covassin, Dolly Maiti, Laura Ortega Aviles, meghna mansukhani, Francisco Lopez-Jimenez, Virend Somers, Amanda Bonikowske
Journal: Circulation (2024)

Introduction: Sleep duration is now recognized as an important determinant of cardiovascular (CV) health. Recently, the CV implications of day-to-day variability in sleep duration have become apparent, with irregular sleep duration associated with increased risk of CV disease, including hypertension. However, the relationship between sleep duration variability and ambulatory blood pressure (BP) patterns in the general population or in patients with CV disease is unknown. Research Questions: We sought to investigate whether irregular sleep duration is associated with aberrant ambulatory BP or heart rate (HR) profiles in patients undergoing cardiac rehabilitation (CR). Methods: We recruited a sample of 42 patients with coronary artery disease enrolled in CR at Mayo Clinic Rochester. Participants underwent 24-hour ambulatory BP monitoring and sleep assessment including one week of wrist actigraphy and sleep diary prior to entering CR. Twenty-four hour, awake, and asleep averages were calculated for systolic BP, diastolic BP, and HR. Nocturnal dipping and morning surge were also computed for BP and HR. Sleep regularity was quantified by SD of actigraphy-derived sleep duration and irregular sleep duration was defined as SD &gt;1 hour. Chi-square tests and Mann-Whitney U tests were used to compare groups. Results: Thirty-six participants (22% females, median age [25 th ,75 th IQR] 66.5 [61,75.8] years, body mass index 31.7 [26.9,35.1] kg/m 2 ) had valid actigraphy and ambulatory BP recordings. We found sleep duration SD &gt;1 hour in 36% of them. Demographics and average sleep duration were similar between those with irregular and regular sleep duration (all Ps&gt;0.11). Twenty-four-hour, awake and asleep HR values were comparable between groups (all Ps&gt;0.26). Participants with irregular sleep duration exhibited lower nocturnal HR dipping (9.2 [3.1,11.6] % vs 12.9 [8.9,18.2] %, P=0.019) than their counterparts with regular sleep. Morning HR surge was also attenuated in patients with irregular sleep duration (3 [-1,9] bpm vs 10 [7,14] bpm, P=0.006). Ambulatory SBP and DBP measures did not differ significantly between groups (all Ps&gt;0.17). Conclusions: High day-to-day variability in sleep duration is linked to blunted nocturnal dipping and morning surge in HR in patients with coronary artery disease enrolled in CR. Because altered ambulatory HR profile predicts unfavorable CV outcomes, evaluation of sleep patterns in the CR setting may yield important prognostic information.
Abstract 4144031: Colchicine for prevention of pericarditis after catheter ablation: A systematic review and meta-analysis.
Authors: Doaa Mashaly, Ayman Hassan, Ruaa Mustafa Qafesha, Menna Elbadry, Muhi Dervis, Ahmed Mohamed, Ahmed Abdelaziz, Shrouk Ramadan, Basel Abdelazeem, Carl LAVIE, Leandro Slipczuk
Journal: Circulation (2024)

Introduction: Catheter ablation (CA) therapy is well established therapy for different types of atrial fibrillation, with some concern including post ablation pericarditis which increases the morbidity and mortality. Colchicine, known for its anti-inflammatory effects has shown to be effective in reducing the incidence of perioperative AF after cardiac surgery. However, the efficacy of post ablation colchicine is still debatable. We aimed to establish evidence on the use of colchicine for preventing pericarditis after catheter ablation. Methods: We searched PubMed, Scopus, WOS and Cochrane until May 2024 for relevant studies that assessed colchicine after CA. The primary outcome of interest was the incidence of pericarditis following AF. Other secondary outcomes were the incidence of pericardial effusion, GI adverse events, and hospitalization rates. Results: A total of nine studies were included with a total of 2795 patients aged 66 to 69.4 years, Colchicine administration before catheter ablation showed a significant decrease in the occurrence of clinical pericarditis after AF ablation compared to placebo (RR=0.38; 95% CI: 0.27, 0.53). Moreover, colchicine was favored to decrease the incidence of AF recurrence rate at 3, 6, and 12 months with the following values, respectively (RR=0.58, 95% CI: 0.42 to 0.80, 0.69, 95% CI: 0.5 to 0.97, and 0.76, 95% CI: 0.66 to 0.87). On the other hand, colchicine was associated with a significant increase in GI adverse events (RR= 2.62, 95% CI: 1.57, 4.37). Conclusion: Colchicine was found to be a promising intervention for reducing the incidence of pericarditis following atrial fibrillation ablation. Despite some contradictory data about gastrointestinal side effects, cautious dosage measures, such as weight-adjusted doses, may improve tolerability while maintaining efficacy in reducing post-ablation events.
Abstract 4143915: A Case of Double Chambered Right Ventricle Associated with Ventricular Septal Defect- an Overlooked Congenital Heart Disease
Authors: Roy Wang, Ammar Abdulfattah, Wayne-Andrew Palmer, Harshith chandrakumar, Michael Schaible, Elizabeth Allison, Monica Thambireddy, Ekenedilichukwu Nnadi, Anna Nevolina, Asher Gorantla, Adam Budzikowski, Suzette Graham-Hill, Inna Bukharovich
Journal: Circulation (2024)

Case description: A 68-year-old man with history of prostate cancer, anal and scrotal squamous cell carcinoma presented to the cardiology clinic with dyspnea on exertion with exercise tolerance limited to 2 flights of stairs. Physical examination showed grade 3/6 holosystolic murmur best heard at the left lower sternal edge. A transthoracic echocardiograph (TTE) revealed an ejection fraction of 65%, prominent muscle bound right ventricular outflow tract obstruction (RVOT) consistent with double chambered right ventricle (DCRV), and a Windsock deformity of the membranous interventricular septum through which there was a VSD with left to right shunting. The maximal pressure gradient across the VSD was approximately 116mmHg. The pulmonary artery systolic pressure was 61mmHg; consistent with severe pulmonary artery hypertension. Discussion: DCRV is a rare condition accounting for 0.5 to 2% of congenital heart diseases. It is characterized by abnormal muscle bands that divide the right ventricle into two chambers; a proximal high-pressure and distal low-pressure chamber, leading to progressive right ventricular outflow tract obstruction (RVOT). This condition rarely occurs in isolation and is often ventricular septal defect (VSD), which is seen in up to 90% of DCRV cases. DCRV may go undiagnosed until adulthood. As the degree of RVOT increases, patients present with shortness of breath and decreased exercise tolerance. TTE is an invaluable tool for diagnosing and determining the severity of obstruction through pulsed and continuous wave doppler to measure the gradient across the hypertrophied muscle bundles. Current guidelines recommend surgery in asymptomatic patients with severe right ventricular obstruction with a pressure gradient greater than 40 mmHg between the proximal and distal compartments within the right ventricle. Even though our patient was mildly symptomatic, his significant pressure gradient of 116 mmHg warrants surgical evaluation. Conclusion: DCRV is a rare and often overlooked congenital heart disease. The patient, despite mild symptoms, exhibited classic features of DCRV and associated VSD, highlighting the potential for this condition to persist undiagnosed into late adulthood. The presence of severe pulmonary hypertension further emphasizes the importance of early detection and ongoing management to prevent severe complications such as heart failure and sudden cardiac death.
Abstract 4143942: Diabetes Education on Cardiovascular Disease Shows Improvements in Knowledge, Confidence, and Intent
Authors: Patrick McWeeny, Kylie Picou, Oge Okeke, Divya Madhusudhan, CarriAnne Crabill, Kaitlyn Lippold, Meg Yuan
Journal: Circulation (2024)

Introduction: Cardiovascular disease is the leading cause of death for people living with type 2 diabetes. Know Diabetes by Heart (KDBH) is a program jointly implemented by the American Heart Association (AHA) and the American Diabetes Association to reduce cardiovascular death, heart attack, heart failure and stroke in people living with type 2 diabetes. We aim to understand knowledge, confidence, and intent changes among program participants in lessons taught through community-based organizations (CBOs) and an online education module. Methods: The AHA collected pre-post data from persons with diabetes and caregivers present at diabetes education courses at participating CBOs and users who participated in the e-module on AHA’s website. Analysis utilized both summary statistics and paired Wilcoxon Signed-Rank testing for significance. Results: Participants at CBOs were generally female (73%), White (43.5%) or Black/African American (36%), non-Latinx (72%), and between 45-69 years old (48%). E-module participants were generally female (69%), White (63.7%), non-Latinx (87%), and between 55-74 years old (48%). After participating in the program, 91% of e-module participants were comfortable speaking with a health care professional about their diabetes and risk for heart disease, and 84% felt it was important to do so. Most participants in the education courses at CBOs were confident in speaking with a health care professional (85%), and in making lifestyle changes (84%) – 11-point improvements. Participants also indicated they were likely to speak with a health care professional about reducing their risk for heart disease and stroke at their next appointment (77%) – a 9-point improvement. None of these changes were statistically significant when pre- and post-tests were paired and analyzed. Respondents scored very high on pre knowledge questions, leaving no room for statistically significant improvement. This may relate to the low difficulty level of predictable questions rather than proficient diabetes knowledge. Confidence and intent showed noticeable improvements over baseline testing. Significance: The KDBH program’s patient education resources improved persons with diabetes and caregivers’ confidence and intent to talk with their healthcare professional about the risk for cardiovascular disease and their diabetes care. One area for improvement is knowledge testing as the survey tools were unable to capture a knowledge level consistent with the literature.
Abstract 4143869: Leveraging ACHD Patients’ Perceptions of Their Illness to Enhance Patient Engagement and Tailor Provider Care Recommendations
Authors: Katelyn Macholl, megumi okumura, Karina Buenrostro, Juhi Mehta, Aleah Sparks, Pranav Ahuja, Kevin Sun, Daniel Dohan, Michelle Gurvitz, Anushree Agarwal
Journal: Circulation (2024)

Introduction: Previous research has described barriers and facilitators for adherence to care guidelines among adults with congenital heart disease (CHD). However, uncertainty remains on how to best support patients in clinical practice within time and resource constraints. Aim: To examine how patients incorporate CHD into their identity and how that influences the management of their condition. Methods: We conducted 48 semi-structured qualitative interviews with adult CHD patients and providers (cardiologists, nurses, patient coordinators, and social workers). Purposive sampling was used to gain patient diversity in CHD lesions, race/ethnicity, SES, geography, and prior gaps in care. Interviews were conducted by a single interviewer using a semi-structured guide based on the “Capability, Opportunity, Motivation-Behavioral (COM-B)” Framework to explore perceived determinants of behavior for managing CHD and navigating the adult health system. Rapid qualitative analysis was conducted to develop two structured data matrices displaying themes about the influence of CHD on identity and enablers of patient engagement. Results: Of 31 patients, 39% were male, 58% were People of Color, and 35% had prior gaps in care (of 3 or more years). Five domains (from 15 themes) emerged to characterize how patients viewed CHD as influencing their ability to engage with care. Themes included 4 Illness Identity domains (Rejection, Acceptance, Engulfment, and Enrichment) and a fifth domain of Indifference - characterized by a lack of emotional valence that accompanies the other four domains. Variance in these domains could be tracked to differences in patient outcomes, such as perceived ability to navigate the healthcare system (Figure 1). Providers and patients demonstrated concordance regarding the perceived influence of illness domains on patients’ mental health but less concordance regarding its impact on patient engagement and healthcare navigation. Conclusion: Considering the extent to which a patient views their CHD as a component of their identity could help providers support adult CHD patient engagement, tailor counseling about care guidelines, and likely enhance the effectiveness of patient-provider relationships.
Abstract 4143940: Circulating Mitochondrial DNA: Biomarker and Inflammation Mediator in Cardiac Ischemia/Reperfusion Injury
Authors: Yuxin Chu, Yutao Hua, Lihao He, Yunxi Chen, Jin He, kameron mckinney, martin young, Scott Ballinger, hui hu, Hind Lal, Min Xie
Journal: Circulation (2024)

Introduction: Ischemia/reperfusion (I/R) injury occurs after coronary revascularization, contributing to infarct size. Circulating mitochondrial DNA (mtDNA) levels are elevated in acute myocardial infarction (MI) patients, and act as Damage Associated Molecular Patterns (mtDNA DAMP), which are recognized by the Toll-like receptor 9 (TLR9), initiating pro-inflammatory responses. Prior studies have shown that loss of TLR9 prevents I/R injury in isolated mouse hearts. However, mtDNA DAMP levels have not been measured in ST-elevation MI (STEMI) patients, and whether blocking TLR9 in mice can reduce I/R injury remains unknown. Hypothesis: MtDNA DAMP levels serve as markers of STEMI related cardiac injury. Blocking the activation of TLR9 will decrease cardiac I/R injury. Methods: MtDNA DAMP levels in serum were measured pre- and 24 hours post- PCI in 55 STEMI patients and 37 healthy controls by qPCR. To evaluate the role of TLR9 on I/R injury, ODN2088 was used to block TLR9 receptor, wild type and TLR9 germline KO mice were subjected to close-chest I/R surgery with minimal systemic inflammation. The cardiac systolic function and infarct size were assessed. Immune cells were isolated from the injured left ventricle and spleens and detected by flow cytometry. Results: Pre- PCI mtDNA DAMP levels were increased ~200 folds in STEMI patients compared to healthy controls. After PCI, the elevated mtDNA DAMP levels reduced significantly, while the troponin T levels increased, suggesting mtDNA is an early marker of MI. Compared with negative ODN, ODN2088 treatment at reperfusion reduced infarct size and total leukocytes, myeloid cells, neutrophils and TNF-α + cells, and a trend of reduced IL-1β + cells, and there was no difference in IL-6 + cells, total macrophages and residential macrophages. Loss of TLR9 in male and female mice significantly reduced infarct size by ~40% and preserved the systolic function. Meanwhile, there is no difference between genders. Conclusions: Circulating mtDNA DAMP level is an early marker of STEMI and may predict the success of PCI. Blocking the mtDNA DAMP-TLR9 signaling pathway during reperfusion significantly reduces I/R injury, indicating it is a viable therapy to mitigate cardiac I/R injury after prompt coronary revascularization.