tbuckley/cabot-search huggingface dataset:
Abstract 4141293: Prognostic Significance of Exercise-Induced Ventricular Arrhythmia Patterns in <i>PKP2</i> -Mediated Arrhythmogenic Cardiomyopathy
Authors: Matteo Castrichini, Raquel Neves, Ramin Garmany, Thomas Allison, Michael Ackerman, John Giudicessi
Journal: Circulation (2024)

Background: Although exercise stress testing (EST) has shown to unmask latent electrical substrates in PKP2 -mediated arrhythmogenic cardiomyopathy (ACM), the prognostic role of EST-induced ventricular arrhythmia (VA) patterns in PKP2-ACM patients is unclear. Objective: To examine the exercise-induced VA patterns observed during EST in PKP2-ACM patients and explore their correlation with major VA outcomes. Methods: We retrospectively analyzed 621 patients with either genotype-positive ACM or genotype-positive dilated cardiomyopathy evaluated between 01/2015 and 04/2024 to identify those with a disease-causative variant in PKP2 (N = 108). After exclusion of 38 PKP2-ACM patients without EST data, demographic and electrocardiographic data was extracted from the electronic medical record. The arrhythmic burden [premature ventricular contractions (PVCs), PVCs in bigeminy, PVC couplets, non-sustained VT (NSVT), sustained VT, ventricular fibrillation (VF), and PVCs/minute] during each EST phase (baseline, peak, active and passive recovery) were reviewed and correlated with major VA outcomes [sudden cardiac arrest (SCA), sustained VT, and appropriate implantable cardioverter-defibrillator (ICD) shocks]. Results: A total of 186 exercise tests from 70/108 (65%) PKP2-ACM patients (mean age 36 ± 20 years, 40 % male) were analyzed. The presence and burden of PVCs occurring singly, bigeminy, couplets. and NSVT were more prevalent during the recovery phase, specifically the passive recovery phase ( Table ). PKP2-ACM patients with structural disease (64%) were more likely to have an increased VA burden during recovery than those without structural disease [28/45 (62%) vs 4/25 (16%); p&lt;0.001]. Interestingly, the presence of an increased arrhythmic burden (worsening PVCs/min or complex PVCs) during the recovery was associated with major VA over a median follow-up of 47 months (HR 8.576 [1.015-72.449]; p= 0.019). Conclusion: Increased arrhythmic burden during the recovery phase (late &gt; early) is associated with an increased risk of major VAs in PKP2-ACM. Further studies are needed to understand if this observation extends to other ACM genotypes and whether EST-induced VA patterns can be used to assess therapeutic efficacy in PKP2-ACM.
Abstract 4140648: Wake up call for the need of standardized medical management for Myocardial Infarction with non-obstructive coronary arteries (MINOCA): A Meta-analysis
Authors: Ayushi Mohan, Arush Rajotia, Sina Bagheri, Keshav Bhattar, Srivaibhav Reddy, Krishna Theja Reddy, Andrew Ho
Journal: Circulation (2024)

Introduction: Myocardial Infarction with non-obstructive coronary arteries (MINOCA) falls on one end of the spectrum of acute myocardial infarction (AMI) and obstructive coronary disease (OCD) falls on the other end. The pathophysiologic mechanisms behind MINOCA include microvascular dysfunction, coronary spasm and plaque rupture without significant luminal obstruction. Despite its apparent benign anatomical findings, it is associated with major adverse cardiovascular events (MACE). Therapeutic strategies to mitigate the risk of MACE are less defined for MINOCA as compared to OCD. Due to various pathological mechanisms behind MINOCA, it is not certain that the classical medical strategies are optimal therefore there is a dire need for a standardized medical management for this subset of patients. Method: Pubmed database was searched using keywords “MINOCA”, “mortality” and “MACE” from 2015 to 2024. All the relevant observational studies were included using PRISMA guidelines. MACE include in-hospital mortality, heart failure, recurrent myocardial infarction (MI) and stroke. Results: 7 relevant observational studies (N= 579,754) were included in the systematic review. A total of 33,050 patients had MINOCA out of which 5862 (18%) suffered MACE. 4 relevant studies were further assessed to check the specific risk of recurrent MI and stroke in MINOCA population. Out of 30,491 MINOCA patients 1095 (3.6%) had recurrent MI and 742 (2.4%) suffered from stroke. The pooled analysis revealed a statistically significant association between MACE and MINOCA patients (Odds ratio [OR] = 1.44, 95% CI: 1.03 - 2.02, p = 0.03). Further sub-analysis also revealed a statistically significant association between recurrent MI (Odds ratio [OR] = 2.05, 95% CI: 1.15 - 3.68, p = 0.02) and MINOCA. Pooled sub-analysis for association between stroke and MINOCA population was also statistically significant. (Odds ratio [OR] = 0.87, 95% CI: 0.81 - 0.94, p = 0.00) Conclusion: Although MINOCA patients experience fewer MACE as compared to OCD patients, they require a specific standardized medical management to address their pathophysiology and its associated substantial cardiovascular risk. Further research is required to prove these results and to elucidate optimal therapies to improve outcome of patients with MINOCA.
Abstract 4141670: A blood test based on RNA-seq and machine learning for the detection of steatotic liver disease: A Pilot Study on Cardiometabolic Health
Authors: Rosana Poggio, Gaston Rodriguez-Granillo, Florencia De Lillo, Bibiana Rubilar, Razan Hijazi, Claudia Solari, Soledad Rodriguez Varela, Alan Mobbs, Estefania Manchini, Ignacio Berdinas, Alejandro La Greca, Carlos Luzzani, Santiago Miriuka
Journal: Circulation (2024)

Background: Whole blood gene expression is modified in response to signals from various tissues, including the liver. Steatotic (fatty) liver disease (SLD) is a hallmark of cardiometabolic disorder strongly associated with vascular disease (50% of patients undergoing coronary angiography). The main goal of this study was to evaluate the classification performance of peripheral whole blood RNAseq analyzed by artificial intelligence (AI) in identifying or ruling out SLD. Methods: The training set consisted of 118 men 40-70 years and women 50-70 years with no history of cardiovascular disease enrolled in a clinical study for assessing coronary artery calcification via a chest computed tomography scan. SLD was defined as &lt;48 Hounsfield Units. Whole blood RNA was isolated and deep sequenced. Different AI models were trained using clinical and transcriptome variables as distinctive features for identifying the presence of SLD. The predictive performance of the combined model (which included transcriptome data, age, sex, BMI, diabetes, and dyslipidemia) was compared against models using only transcriptome data or relevant clinical variables for the presence of SLD. To ensure a robust evaluation of the model's performance, an external validation was conducted using two independent groups (Validation 1 (V1): 32 participants and Validation 2 (V2): 33 participants). Results: The prevalence of SLD was 47.5% in the training set, 50% in V1 and 51% in V2 sets. The population variables were as follows (control versus cases): mean age 56 vs. 57 ys; females 26% vs. 29%; diabetes 16% vs. 25%; hypertension 42% vs. 55%; dyslipidemia 23 vs. 34%; obesity 34 vs.57% (p 0.02) and coronary calcium score (mean 96.1 vs. 131.12 Agatston Units, p 0.08). The combined AI model exhibited the highest accuracy for the presence of SLD in the validation set (V2), achieving an area under the curve (AUC) of 0.96 (95%CI 0.90-1.00), sensitivity of 76%, specificity of 94%, positive predictive value of 93%, negative predictive value of 79%, and overall accuracy of 85%. The combined AI model exhibited significant discrimination improvement over the clinical risk model (AUC=0.83; p&lt;0.011). Conclusions: In this pilot study, a blood test based on whole blood transcriptome, clinical variables, and AI analysis showed better discrimination ability than clinical risk factors for predicting the presence of steatotic liver disease.
Abstract 4140910: New-onset Atrial Fibrillation and Associated Long-Term Cardiovascular Morbidity and Mortality in Patients with Type 2 Diabetes Mellitus; A Meta-analysis of 16 million patients.
Authors: Abhigan Shrestha, Tanzina Afroze, Vikash Jaiswal, Ravi Sankar Reddy Edara, Aman Goyal, Suman Kadariya, Soney Basnyat
Journal: Circulation (2024)

Background: Patients with type 2 diabetes mellitus (T2DM) often develop atrial fibrillation. Nevertheless, its incidence and long-term cardiovascular outcomes in newly diagnosed atrial fibrillation in patients with T2DM are still unclear. Hypothesis: We aim to investigate the association between new-onset AF and the risks of atherosclerotic cardiovascular disease (ASCVD); heart failure (HF), stroke, and all-cause mortality among patients with T2DM. Methods: A systematic search was conducted using multiple electronic databases from inception until March 2024 using the appropriate Mesh terms, “atrial fibrillation,” “diabetes mellitus,” “stroke,” “heart failure,” and “all-cause mortality.” We used the random effect model to calculate the pooled relative risk and their corresponding confidence interval. A p-value of &lt;0.05 was considered statistically significant. Results: A meta-analysis was piloted using 12 studies. Of these, 10 studies studied DM patients versus non-diabetic (6442051 versus 9572901), and two studies compared atrial fibrillation versus non-atrial fibrillation in DM patients (1521 versus 17560) with a mean follow-up of 9.9 years. Pooled analysis showed that patients with T2DM are more likely to develop AF compared to nondiabetic patients (OR: 1.41, 95%CI: 1.18-1.64, p&lt;0.001). Furthermore, patients with type 2 DM with new-onset atrial fibrillation have an increased of developing HF (OR 3.67, 95% CI 3.07-4.27, p&lt;0.001), stroke (OR 1.79, 95% CI 1.40-2.18, p&lt;0.001), and all-cause mortality (OR 1.70, 95% 1.42-1.98, p&lt;0.001). Conclusion: This study reveals that patients with type 2 DM are at increased risk of developing atrial fibrillation compared to nondiabetic patients. Long-term cardiovascular morbidity, such as heart failure, stroke, and all-cause mortality, are also high in patients with type 2 DM with new-onset atrial fibrillation.
Abstract 4140664: From Atrial Fibrillation to Rare Genetic Disorder: The Unexpected Diagnosis of Birt-Hogg-Dubé Syndrome
Authors: Morgan Casper, Hannah Bernstein, Uma Srivatsa
Journal: Circulation (2024)

Introduction: Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal-dominant disorder due to mutations in the FLCN gene. As an AMPK-mTOR interacting molecule, this loss-of-function mutation impacts energy homeostasis leading to uninhibited cell growth. While studies have linked this genetic mutation to severe cardiac hypertrophy, a connection to persistent atrial fibrillation (AF) is unestablished. We present a case in which an individual's initial symptoms of AF ultimately led to a diagnosis of BHDS. Case Summary: A 56-year-old male with a history of “holiday heart syndrome” presented for an AF consultation. Despite alcohol cessation, he continued to have paroxysmal AF with severe fatigue and palpitations. After three unsuccessful cardioversions and refractory episodes despite Dronedarone therapy, he was scheduled for an ablation. A pre-procedural transesophageal echocardiogram showed a left ventricular (LV) ejection fraction of 55%, mild concentric LV hypertrophy, and mild left atrial enlargement. These enlargements were new compared with imaging one year prior. A cardiac gated CT detailed the pulmonary vein structure and incidentally revealed bilateral cystic lung changes, leading to a pulmonology referral. Despite an initial successful ablation targeting the pulmonary vein, his symptoms returned within days. He was loaded with amiodarone. Monitoring on his apple watch showed a high burden of AF. He underwent a repeat ablation to achieve complete pulmonary vein isolation with improvement in his symptoms. Further pulmonary evaluation highlighted a family history of spontaneous pneumothorax and a dermatology consultation then confirmed BHDS via fibrofolliculoma biopsy. Discussion: This case underscores the importance of comprehensive evaluations, revealing a rare genetic disorder from an initial AF assessment. While no definitive link exists between BHDS and cardiomyopathy, we aim to understand possible connections between this rare condition and its systemic cardiovascular impacts. We propose that upregulation of mTORC1 activity and attenuation of AMPK from the loss of function of FLCN lead to uncontrolled cell division and left ventricular hypertrophy. This hypertrophy then results in left atrial dilation, contributing to the development and persistence of AF. Given the rarity of this condition, more research is needed on symptom onset and systemic linkages. Swift diagnosis from incidental findings are crucial for managing symptoms and the underlying disease.
Abstract 4140727: Genetic Insights into Chronic Thromboembolic Pulmonary Hypertension: Uncovering Immune Mechanisms in the Chinese Population
Authors: mengjie duo, Bingzhang Zou, Zhu Zhang, Zhenguo Zhai, Chen Wang
Journal: Circulation (2024)

Background: Current genomics studies on chronic thromboembolic pulmonary hypertension (CTEPH) have primarily focused on European populations, with limited research conducted on East Asian populations. Although CTEPH is considered a complication of acute pulmonary thromboembolism (PTE), 25% of CTEPH have no prior history of PTE. Aim: This study aimed to uncover the genetic basis of CTEPH and identify susceptibility loci and genes from the Chinese population, seeking to understand the shared and distinct genetic mechanisms between CTEPH and PTE. Methods: The discovery cohort enrolled 412 CTEPH and 2000 controls for whole genome sequencing. Genome-wide association analysis (GWAS) and gene annotation were performed for common variants (MAF&gt;5%) to identify susceptibility gene. The heritability of CTEPH was calculated using LDSC. Additionally, burden test was performed in rare variants (MAF&lt;1%) to identify candidate genes. Bulk and single-cell transcriptome analyses were performed on PEA tissues from CTEPH and controls. Method scPagwas was used to integrate GWAS and transcriptomics data. Results: A total of 1379 SNPs reached genome-wide significance (P&lt;5×10 -8 ), and 217 risk loci were identified after Clumping. LDSC estimated a heritability of 0.1217 for CTEPH. FUMA and TWAS analysis mapped 708 susceptibility genes, of which 95 genes were suggested by both common and rare variants. Several CTEPH susceptibility genes, including CYP27C1, PROC, F2, LRP4, MPHOSPH9, SBNO1, EDEM2, PROCR, and ABO , have been previously reported to be associated with VTE. However, only ABO, F2 , and HLA-DRA overlap with CTEPH susceptibility genes identified in European populations. The scPagwas indicated that monocyte-macrophage trait correlation scores were highest in the single cell profiles of CTEPH. The differentially expressed genes from transcriptomics and susceptibility genes, identified five key genes: SLC11A1, SLCO2B1, RILPL2, HCK , and CTSS . SLC11A1 is primarily distributed in monocytes and macrophages and regulates multiple immune inflammation processes, including reactive oxygen species and interleukin production, and T cell differentiation. Disease-related pathways encompass the complement coagulation pathway, Th cell differentiation, and various autoimmune diseases. Conclusion: CTEPH is influenced by genetic factors. Multiomics data suggest that abnormal immune responses mediated by high SCL11A1 expression in monocytes and macrophages may be a key mechanism in the development of CTEPH.
Abstract 4141159: Trends in Obesity Related Ischemic Heart Disease Mortality Among Adults in the United States from 1999 to 2020
Authors: Muhammad Umer Sohail, Muhammad Saad, Muhammad Sameer Arshad, Muhammad Ovais Sohail, Aymen Ahmed, Aima Azhar, Pankaj Kumar, Muhammad Memon, Izza Shahid
Journal: Circulation (2024)

Background: Obesity is a significant risk factor for ischemic heart disease (IHD) with increasing prevalence denoted in the recent decade. This study examines the temporal trends in obesity-related IHD mortality in the U.S. from 1999 to 2020. Methods: We used Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) Multiple cause of death database to analyze obesity related IHD mortality in adults ≥ 25 years old. We examined IHD as the underlying cause and obesity as a contributing cause. Age-adjusted mortality rates (AAMRs) and Crude mortality rates (CMRs) per 100,000 persons were calculated. Joinpoint regression was used to assess the trends and calculate annual percent change (APC) to examine trends overall, and across demographic (age, sex, race) and geographic regions. Results: A total of 139,644 obesity-related IHD deaths were identified. Overall, AAMR increased from 1.92 in 1999 to 4.69 in 2020. AAMRs showed a consistent rise between 1999 and 2018 (APC: 4.00 [95% CI: 2.85 to 4.44]), followed by a marked increase from 2018 to 2020 (APC: 9.87 [95% CI: 4.46 to 12.75]). AAMR was higher in males (3.79) than females (2.10). Black populations had the highest AAMR (4.06), followed by White populations (2.08) and Hispanic/Latino populations (1.94). Older adults (age 65+ years old) had the highest CMR (5.73), followed by middle-aged adults (age 45-64 years old, CMR: 4.31) and young adults (age 25-44 years old, CMR: 0.73). AAMR was higher in nonmetropolitan areas (3.47) compared to metropolitan areas (2.78). States in the top 90th percentile for AAMR were Vermont, Oklahoma, California, North Dakota, and Colorado, while those in the bottom 10th percentile were South Carolina, Massachusetts, Utah, Connecticut, and Alabama. Conclusion: Obesity-related IHD has increased drastically in the U.S. throughout the study period. Further research is needed to comprehend these trends and to help develop preventative tactics.
Abstract 4141008: A Rare Case of Epicardial Cavernous Hemangioma with Coexisting Severe Mitral Regurgitation
Authors: Ala Abdallah, Jenna Sutton, Nazanin Houshmand, Neelesh Gupta, Chowdhury Ahsan
Journal: Circulation (2024)

Background: Primary cardiac tumors are rare, occurring in 0.001% - 0.03% of the general population, most discovered at autopsy. Approximately 75% of these tumors are benign, of which 2% represent cardiac hemangiomas. While most cardiac tumors are silent, devastating clinical symptoms have been documented including cardiac tamponade, arrhythmia, stroke and death. Such presentations may manifest at any age and are related to the tumor’s size and location. Case Description: A 68-year-old male with a history of OSA was referred to cardiology by his primary care provider after an incidental finding of left ventricular hypertrophy on EKG. Examination was significant for a grade III late systolic murmur. Echocardiography revealed severe mitral regurgitation, mitral valve (MV) prolapse and an epicardial mass suggestive of a tumor. Cardiac CT demonstrated an epicardial tumor of the left atrial appendage, uplifting the left main coronary artery, displacing the proximal LAD and first diagonal branch (Diag) (figure 1). Cardiac catheterization ruled out significant CAD, but identified tumor blush from the Diag (Figure 2a). Surgical intervention, including MV repair, was successful. Resection of the mass required extrication from the Diag, the proximal LAD and 1st septal branches, which was performed without compromise of coronary vessels. Pathology confirmed a diagnosis of epicardial cavernous hemangioma (Figure 2b). Patient is doing well 1 year post intervention. Discussion: This case illustrates the diagnostic and therapeutic challenges of primary cardiac tumors. As with our patient, cardiac tumors are often found incidentally. However, surgical resection is recommended as the consequences of tumor growth and/or invasion into surrounding structures is unpredictable and poses a significant morbidity and mortality risk. Comprehensive imaging and an interdisciplinary collaboration between medical and surgical personnel is essential for timely diagnosis and appropriate treatment planning.
Abstract 4141390: A quality improvement intervention and academic detailing vs. academic detailing alone, a randomized quality improvement study
Authors: Jeremy Sussman, Richard Evans, Brittani Garlick, Geoffrey Barnes, Arthur Allen, David Parra, Jennifer Burns, Jacob Kurlander
Journal: Circulation (2024)

Background: Appropriate direct oral anticoagulants (DOAC) dosing could improve their safety and effectiveness. To address this, we developed an intervention to improve on-label dosing using academic detailing and a quality improvement intervention. Methods: This was a cluster RCT with clusters at the site level. There were 2 arms, academic detailing (AD) and AD plus Learn. Engage. Act. Process. (AD/LEAP). Interventions: Primary care doctors and anticoagulation pharmacists from all participating sites were invited to participate in academic detailing, a 1:1 educational and motivational coaching program, about ways to improve DOAC prescribing safely. Intervention arm sites were also invited to participate in LEAP, a quality improvement program based on plan-do-study-act cycles. Sites: 8 VA medical centers Inclusion criteria: All patients on DOACs at participating sites. Analysis: Generalized Estimating Equations with logit links and clusters at the facility level using aggregated proportion data. Models were weighted by the size of the denominator within each facility and longitudinal measurements were modeled with an autoregressive working correlation matrix. For difference-in-difference modeling, the 6-month pre- and post-period data were included and entered into the model as a fixed effect plus an interaction with the treatment arm. Outcomes: The primary outcome was the percentage of DOAC prescribing that was off-label, including under- and over-dosing for that individual and using for inappropriate indications. Results: Over the full length of the study, there were 34,127 patients on DOACs across the 8 sites. The percentage of prescriptions that met the primary outcome increased from 5.65 to 6.43 in the AD arm and from 5.9 to 6.43 in the AD+LEAP arm, yielding a difference-in-difference of -0.25 (95% CI -1.57- 1.06). An as-treated analysis, which dropped the two sites that did not finish their LEAP programs, also found no effect, as did sub-groups of impacts on patients whose reason for using DOACs was atrial fibrillation vs. thromboembolism. Discussion: A quality improvement intervention did not improve safe DOAC prescribing when added to an academic detailing intervention. We hypothesize the primary reason was insufficient engagement with the intervention.