tbuckley/cabot-search huggingface dataset:
Abstract 4142141: The Genetic and Phenotypic Determinants of Life-Threatening Arrhythmias in Pediatric Bileaflet Mitral Valve Prolapse Arrhythmia Syndrome
Authors: Saige Mitchell, Henry Foote, Ghaith Sharaf Dabbagh, Andrew McCrary, Anwar Chahal, Andrew Landstrom
Journal: Circulation (2024)

Background: Bileaflet mitral valve prolapse (BMVP) is a rare disease in the pediatric population. It may be a proarrhythmic substrate, particularly when present with mitral annular disjunction (MAD). There is less known about the genetic etiology and phenotypic spectrum of patients diagnosed with BMVP in childhood. Objective: To determine the genetic and phenotypic factors that influence arrhythmia development and cardiac arrest in pediatric patients with BMVP. Methods: We established a cohort of pediatric probands with at least one clinical encounter at Duke University Hospitals. Patients were categorized by underlying cardiac condition leading to groups of idiopathic BMVP, aortopathies, cardiac channelopathies/cardiomyopathies, and congenital heart disease (CHD). We grouped patients by presence of MAD. Primary outcome was ventricular arrhythmias. Secondary outcomes were cardiac arrest, pacemaker or implantable cardioverter defibrillator (ICD) placement, and secondary cardiac surgery. Rates of arrhythmia and secondary outcomes were compared using Fisher’s exact test. Freedom from event curves were generated to track first arrhythmia episodes and age at diagnosis and compared using a log-rank test. Results: 54 pediatric patients were included with 30 (55.6%) female and an average age at diagnosis of 8.2 years. Patients with concurrent CHD had earlier BMVP diagnosis compared to those with idiopathic BMVP and cardiac channelopathies/cardiomyopathies (p &lt; 0.05). Yield of gene panel testing was 71.88% LP/P overall, 56.25% in isolated BMVP, and 12.5% in MAD. Among the pathogenic variants found in MAD, 60% were aortopathy genes, 20% cardiomyopathy/channelopathy genes, and 20% in sudden unexpected death in epilepsy genes. The most common arrhythmia was ventricular tachycardia found in 52% of arrhythmia episodes, followed by supraventricular tachycardia (19%), and ventricular fibrillation (15%) which only was seen in MAD. The rate of arrhythmia in MAD was higher (55%) compared to 14% in patients with isolated BMVP (p &lt; 0.001), and rates of breakthrough arrhythmia were similar between groups. Patients with MAD had a rate of 27.27% for pacemaker or ICD placement compared to 2.33% in patients with isolated BMVP (p &lt; 0.05). Conclusions: BMVP is likely a common phenotype with a variety of genetic and phenotypic subtypes. Presence of MAD increases risk of arrhythmia and need for a pacemaker or ICD in patients with BMVP independent of the underlying cardiac condition.
Abstract 4142105: Impact of Supraventricular Tachycardia on Pregnancy Outcomes
Authors: Arya Ardehali, Marla Kiess, Valerie Rychel, Amanda Barlow, Jennifer Oakes, Marc Deyell, Jasmine Grewal
Journal: Circulation (2024)

Background: Paroxysmal supraventricular tachycardia (PSVT) is one of the most common arrhythmias among pregnant women, in part due to the maternal physiological changes that occur during pregnancy. However, studies investigating the risk of new-onset and pre-existing PSVT in pregnancy, and the associated adverse maternal and fetal/neonatal outcomes are lacking. Research Questions: This study aimed to determine: 1) the proportion of women presenting with new-onset PSVT in pregnancy; 2) the impact of prior PSVT history on episode severity and management during pregnancy; and 3) the rate of adverse maternal and fetal/neonatal events among women with PSVT in pregnancy. Methods: Prospective case-control study: 77 consecutive pregnancies in 75 women referred to the St. Paul’s Hospital Cardiac Obstetric Clinic between January 2010 and January 2022 secondary to findings consistent with or a history of atrioventricular nodal re-entrant tachycardia (AVNRT) and atrioventricular re-entrant tachycardia (AVRT) PSVT without documented structural heart disease. Maternal cardiac, obstetric, and fetal/neonatal adverse events were compared to a control group consisting of 57 women with low risk, normal pregnancies and no cardiac diagnosis. Results: Among the PSVT cohort (n=77), 63 (82%) pregnancies had a prior diagnosis of PSVT and 18% were new-onset in pregnancy. Sixty-eight percent of those with a prior PSVT diagnosis had recurrence in pregnancy. Those with a more recent history (within 5 years of pregnancy) were more likely to experience PSVT during pregnancy compared to those with a more remote history (81% vs. 31%, p&lt;0.001). Similarly, they experienced a higher frequency of PSVT during pregnancy and increased rates of chemical cardioversion (38% vs. 12%, p=0.05). There was a higher rate of adverse obstetrical events in the PSVT group vs. controls (8% vs. 0%, p=0.03), however this is likely due to higher prevalence of obstetric risk factors among the PSVT cohort. Adverse fetal/neonatal events were similar between the PSVT group vs. controls (17% vs. 19%, p=0.72). Conclusions: PSVT events were safely managed in pregnancy with no major adverse cardiac events and similar fetal/neonatal outcomes as healthy controls. However, recurrence and burden of PSVT during pregnancy is frequent and leads to management complexities among those with a history of PSVT, reinforcing the need for pre-pregnancy counselling and catheter ablation for definitive management of PSVT prior to pregnancy.
Abstract 4142147: Clinical Outcomes in Patients with Atrial Fibrillation and End-Stage Renal Disease Managed with Rivaroxaban versus Warfarin; A Propensity-Score Matched Analysis
Authors: Alexander Somerville, Anderson Anuforo, Bharat Rawlley, Auyon Ghosh
Journal: Circulation (2024)

Introduction: The utilization of direct oral anticoagulant (DOAC) agents for atrial fibrillation (AF) in individuals with end-stage renal disease (ESRD) has increased despite a lack of robust supportive data from randomized controlled trials. We planned to assess the outcomes associated with rivaroxaban versus warfarin in the ESRD population with AF. Methods: We utilized the TriNetX Global Collaborative Network, which includes 114 Healthcare organizations to perform a propensity-score matched retrospective cohort study. We used ICD-10 codes to identify individuals with ESRD and AF, over 18 years of age, excluding those with prosthetic valves and apixaban or edoxaban use. Data were collected from 2011 to 2024. We evaluated the incidence of ischemic stroke (I63), intracranial hemorrhage (I62.9), cardiac arrest (I46), mortality, gastrointestinal (GI) hemorrhage (K92.2), systemic embolism and thrombosis (I74.3, I74.2), and other cardiac arrythmias (I49). We performed propensity-score matching (PSM) on age, sex, race, BMI , hypertension, diabetes mellitus, tobacco use, heart failure, stroke, or acute myocardial infarction. Results: We identified 25,092 individuals in the warfarin group and 2,391 individuals in the rivaroxaban group. After PSM, 2,381 individuals remained in each group. The average age was 72.9, predominantly male (59.8%), with 62.9% white, 14.7% African American, and 6.5% Hispanic individuals. Compared to those treated with warfarin, individuals treated with rivaroxaban demonstrated a lower risk of a composite outcome (Infarct, intracranial hemorrhage, mortality) (RR 0.823, 95% CI 0.765-0.885), mortality (RR 0.830, 95% CI 0.775-0.888), GI hemorrhage (RR 0.566, 95% CI 0.439-0.730), and cardiac arrest (RR 0.696, 95% CI 0.531-0.911). We found no significant difference in the risk of ischemic stroke (RR 1.024, 95% CI 0.744-1.408), intracranial hemorrhage (RR 0.587, 95% CI 0.270-1.280), systemic embolism (RR 0.828 (95% CI 0.512-1.339), or other cardiac arrythmias (RR 0.973, 95% CI 0.804-1.179). Conclusion: In individuals with AF and ESRD the use of rivaroxaban, in comparison to warfarin, was associated with a reduction in the risk of mortality, gastrointestinal hemorrhage, and cardiac arrest. We found no difference in other clinically relevant outcomes, including ischemic stroke. These findings suggest an extension of the safety benefits previously observed with DOACs to the ESRD population, however further research is needed to guide management.
Abstract 4141994: Targeted Atrial Fibrillation Screening in Older Adults: A Secondary Analysis of the VITAL-AF Trial
Authors: Sachin Shah, Jay Iyer, Leila Agha, Yuchiao Chang, Steven Atlas, Jeffrey Ashburner, David McManus, Patrick Ellinor, Steven Lubitz, Daniel Singer
Journal: Circulation (2024)

Background: Screening trials for atrial fibrillation (AF) have produced mixed results; however, it is unclear if there is a subset of individuals for whom screening would be effective. Identifying such a subgroup would support targeted screening. Methods: We conducted a secondary analysis of VITAL-AF (NCT03515057), a randomized trial of one-time, single-lead ECG screening during primary care visits. We tested two approaches to identify a subgroup that would benefit from screening (i.e., heterogenous screening effects). First, we use a potential outcomes framework to develop an effect-based model. Specifically, we predicted the likelihood of AF diagnosis under both screening and usual care conditions using LASSO, a penalized regression method. The difference between these probabilities was the predicted screening effect. Second, we used the CHARGE-AF score, a validated AF risk model. We used interaction testing to determine if the observed diagnosis rates in the screening and control arms were statistically different when stratified by decile of the predicted screening effect and predicted AF risk. Results: Baseline characteristics were similar between the screening (n=15187) and usual care (n=15078) groups (mean age 74 years, 59% female). On average, screening did not significantly increase the AF diagnosis rate (2.55 vs. 2.30 per 100 person-years, rate difference 0.24, 95%CI -0.18 to 0.67). Patients in the highest decile of predicted screening efficacy (n=3026, 10%) experienced a large and statistically significant increase in AF diagnosis rates due to screening (6.5 vs. 3.06 per 100 person-years, rate difference 3.45, 95%CI 1.62 to 5.28; interaction p-value 0.038) ( Figure 1 ). In this group, the mean age was 84 years and 68% were female. Participants in the highest decile of AF risk using the CHARGE-AF score did not have a statistically significant increase in AF diagnosis rates due to screening ( Figure 2 ). Predicted screening effectiveness and predicted AF risk were poorly correlated (Spearman coefficient 0.13). Conclusions: One-time screening may increase AF diagnoses in a subgroup of older adults with the largest predicted screening effect. In contrast, predicted AF risk was a poor proxy for predicted screening efficacy. These data caution against the assumption that high AF risk is necessarily correlated with high screening efficacy. Prospective studies are needed to validate whether AF screening is effective in the subgroup identified in this study.
Abstract 4142116: The Association Between Urinary Sodium Concentration (UNa) and Outcomes of Acute Heart Failure in Patients Undergoing Diuretic Therapy: A Systematic Review and Meta-Analysis
Authors: Shehroze Tabassum, Muhammad Khuzzaim Khan, Namra Khalil, Hussam Al Hennawi, Angad Bedi, Alexander Shpilman
Journal: Circulation (2024)

Introduction: The measurement of Urinary Sodium Concentration (UNa) is a pivotal biomarker in managing Acute Heart Failure (AHF), offering a non-invasive and readily accessible means to evaluate diuretic response. This systematic review and meta-analysis is designed to investigate the correlation between UNa levels and patient-centric outcomes in AHF, aiming to validate the evidence base and refine clinical practice. Methods: This systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. We systematically searched PubMed, Cochrane Central, Scopus, Google Scholar, and ClinicalTrials.gov from their inception to May 2024. Our search included randomized controlled trials (RCTs) and observational studies comparing outcomes between acute heart failure (AHF) patients with high urinary sodium concentration (UNa) and those with low UNa. Results: The analysis included 12 studies comprising 5 RCTs and 7 observational studies, incorporating a total of 8,743 AHF patients. In the high UNa group, pooled data demonstrated significantly higher urinary output (MD 534.49 ml, 95% CI 348.48 to 720.49; P &lt; 0.00001) and increased weight loss (MD 1.15 kg, 95% CI 0.45 to 1.85; P &lt; 0.001). Additionally, there was a lower risk of renal function decline (OR 0.48, 95% CI 0.24 to 0.97; P &lt; 0.04). Patients with high urinary sodium had a shorter mean hospital stay of 7.6 days compared to 8.8 days for those with low UNa, with an overall reduction in length of stay (MD -1.38 days, 95% CI -2.44 to -0.32; P &lt; 0.01). Mortality was also lower in the high UNa group, particularly over longer follow-up periods: at 1-month follow-up (OR 0.40, 95% CI 0.21 to 0.78; P = 0.007), at 6-month follow-up (OR 0.45, 95% CI 0.29 to 0.72; P = 0.0007), and at 12-month follow-up (OR 0.16, 95% CI 0.16 to 0.26; P &lt; 0.00001). Furthermore, the high UNa group exhibited a lower risk of worsening heart failure requiring inotropes (OR 0.40, 95% CI 0.23 to 0.70; P = 0.002) and a reduced incidence of heart failure rehospitalization (OR 0.42, 95% CI 0.20 to 0.89; P = 0.02). Conclusion: High urinary sodium concentration is strongly associated with improved clinical outcomes in acute heart failure, including greater urinary output, increased weight loss, shorter hospital stays, and reduced risks of renal function decline, mortality, worsening heart failure, and rehospitalization.
Abstract 4142158: Murmur Detection and Classification Using Signal Processing and Sound Feature Analysis
Authors: Ram Sivaraman, Yizi Xiao
Journal: Circulation (2024)

Introduction: Heart murmurs are abnormal sound signals generated by turbulent blood flow and are closely associated with specific heart disorders. Current methods to detect and qualify murmurs do not recognize that an important part of diagnosing a patient depends upon murmur location in the heart valves and timing between fundamental heart sounds. This research presents HM-Detect, a novel algorithm to provide accurate heart murmur characteristics to cardiologists, specifically in telemedicine. In particular, can we use signal processing and machine learning techniques to detect and classify heart murmur characteristics (e.g. timing and location) from heart sound signals? Approach: HM-Detect analyzes heart sound features, namely the filterbank energies and spectral sub-band centroids. Four separate Random Forest Classifiers (RFCs) were built for each of the four valves of the heart using statistical moments of these features. Additionally, an undersampling technique on heart sound data and a novel “multi-modal” long short-term memory (MMLSTM) neural network incorporate the temporal aspect of heart sounds. The algorithms were validated on signals from the CirCor DigiScope dataset, which is a clinically verified dataset. Three different neural network architectures with varying number of cells and MMLSTM layers were compared. Results and Data Analysis: The feature importance of the first four statistical moments from the RFCs show that the variance has the lowest importance (max value &lt; 0.010) while the mean, skewness, and kurtosis, have higher importance (max value &gt; 0.020). All RFC models were evaluated using the area under their receiver operating characteristic curves (AUROCs). The RFCs were much more successful at classifying murmurs from the pulmonary and tricuspid valves (AUROC = 0.83 and 0.78, respectively) when compared with the aortic and mitral valves (AUROC = 0.72 and 0.65, respectively). Furthermore, the proposed method for murmur timing can achieve a performance accuracy of around 90%, with the best of the three MMLSTM-based models having an F1 score of 0.91 and a test accuracy of 87%. Conclusions: Heart sound features, namely filterbank energies and sub-band spectral centroids, were successfully used to build RFC algorithms which accurately classify murmur locations. The combination of undersampling and MMLSTMs allow for an encapsulation of the spatiotemporal profile of heart sounds and accurately detect and classify heart murmurs based on murmur timing.
Abstract 4141989: Utilization rates of SGLT2 inhibitors and GLP-1 receptor agonists remain significantly lower than those for other cardioprotective medications: Results from a retrospective, cross-sectional study at a large academic medical center
Authors: Andrew Ling, Thomas Mawson, Gaurav Tiwari, Thanh Tram, Tuyen Yankama, Rochelle Rubin, George Silva, Zachary Jonas, Charlotte Ward, Sara Moran, Juweria Quadir, Richard Chaudhary, Frank Qian, Zsu-Zsu Chen, Mark Benson
Journal: Circulation (2024)

Background: Specific sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) significantly improve outcomes in patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) or heart failure. Contemporary data regarding utilization rates of these medications remain limited. Hypothesis: Utilization rates of SGLT2i/GLP-1RA remain low, especially among cardiology providers. Aim: Characterize utilization rates of SGLT2i/GLP-1RA in a large academic medical center (AMC). Methods: We developed algorithms to query electronic health records from Beth Israel Deaconess Medical Center to identify 18-74 year-old patients with either T2D and ASCVD (cohort 1) or patients with heart failure with reduced or preserved ejection fraction (HFrEF/HFpEF, cohort 2) who qualified for SGLT2i or GLP-1RA therapy between 1/1/21-12/31/22 according to 2020 ACC Expert Consensus Decision Pathway and 2021 ADA Standards of Care guidelines. Positive predictive values (PPV) for each algorithm were calculated following manual review of 150 randomly-selected charts from each cohort. Comparisons were performed using Fisher’s exact test. Results: We identified 1,022 patients with T2D and ASCVD (PPV 87.9%) who qualified for SGLT2i and/or GLP-1RA therapy and 2,070 patients with HFrEF or HFpEF (PPV 84.7%) who qualified for SGLT2i therapy. In contrast to utilization rates of statins (89.8%), significantly fewer patients with T2D and ASCVD had received a prescription for a SGLT2i (35.9%, P&lt;0.001), GLP-1RA (39.3%, P&lt;0.001), or either medication (54.6%, P&lt;0.001) any time before 12/31/22. Similarly, compared to utilization rates of ACE inhibitors or ARBs (70.4%), significantly fewer patients with HFrEF/HFpEF had received a prescription for a SGLT2i (30.3%, P&lt;0.001). Cardiology providers were the top prescribers for SGLT2i in patients with HFrEF/HFpEF (48.7% of prescriptions). However, cardiology providers prescribed significantly fewer SGLT2i or GLP-1RA for patients with T2D and ASCVD (8.6% of prescriptions) compared to primary care providers (49.4%, P&lt;0.001). Conclusions: Within a single AMC, utilization rates of SGLT2i and GLP-1RA remain significantly lower than those for other cardioprotective medications. Our data suggest a possible opportunity for cardiology providers to improve utilization of SGLT2i and GLP-1RA. Further study is needed to more broadly characterize these findings.
Abstract 4141966: Myotonic Dystrophy type I (DM1) Impairs Cardiac Bioenergetics and Disrupts Cardiac Mitochondrial Fusion-Fission Dynamics
Authors: Oluwafolajimi Adesanya, Pouya Nabie, Subhashis Natua, Auinash Kalsotra
Journal: Circulation (2024)

Background: DM1 is the commonest cause of adult-onset muscular dystrophy, affecting 1-in-2100 people in the U.S. DM1 is a (CTG)n trinucleotide repeat expansion disease in the 3’UTR of the DMPK gene. Once expressed, the repeat RNA form toxic hairpins, which sequester the muscle blind-like (MBNL) family of splicing factors. This induces tissue-wide disruption of alternative splicing events, resulting in DM1 symptoms, including muscle weakness, neurological defects, and cardiomyopathy. Recent reports have demonstrated impaired mitochondrial function in the brain, skeletal muscle, and fibroblast of DM1 patients, these have however, not been reported in the heart, nor have their potential contribution to the pathogenesis of DM1 cardiomyopathy been explored. Methods: Using an inducible, cardiomyocyte-specific DM1 mouse model (aka MHCrtTA:TRE960i), we performed extracellular flux analysis on cardiac mitochondrial fractions obtained from heart tissue of control and DM1 mice. This was accompanied by quantification of ATP production, to determine oxidative phosphorylation (OXPHOS) efficiency. Further, we performed transmission electron microscopy (TEM) and TOM20 immunofluorescence (IF) microscopy to assess the integrity of mitochondrial network in DM1 mice. Finally, we performed gene expression studies to identify mis-splicing events involving mitochondria-related genes and validated these in heart tissues obtained from both DM1 mice and deceased human DM1 subjects. Results: DM1 induced a multi-state increase in cardiac oxygen consumption rate (OCR) which was however accompanied by decreased ATP levels (2.83µM/10µg vs. 2.45µM/10µg, p =0.0079) indicating reduced cardiac OXPHOS efficiency. DM1 also induced a disruption of mitochondria network, with increased mitochondria fragmentation seen on IF microscopy, and expansion of the intermyofibrillar mitochondria compartment seen on TEM. These findings correlated with the mis-splicing of mitochondrial fission factor (MFF), with an increased skipping of Mff exon 6 in DM1 mice (ΔΨ: -16.8%, p =0.0069) and human DM1 heart tissue (ΔΨ: -19%, p &lt;0.01) compared with controls. Interestingly, this resulted in the increased expression of a shortened 29kDa MFF protein isoform in DM1 mice (Δ%29kDa: 47%, p =0.0003) and human (Δ%29kDa: 21.1%, p &lt;0.0001) heart samples relative to controls. Conclusion: DM1 impairs cardiac bioenergetic function potentially through the mis-splicing of critical genes regulating mitochondrial fusion-fission dynamics.