tbuckley/cabot-search huggingface dataset:
Abstract 4136781: Stethoscopes to Sequencers: How Next Generation Sequencing Aids Pediatric Cardiac Intensive Care Diagnosis
Authors: Angela Onorato, Rachel Gosselin, BIMAL CHAUDHARI, Chance Alvarado, Vidu Garg, Amee Bigelow
Journal: Circulation (2024)

Background: Despite a high burden of rare genetic diseases among children admitted to cardiac intensive care units (CICUs), comprehensive guidelines for genetic testing in children with heart disease, particularly those that are critically ill, are lacking. Traditional testing methods, such as karyotype, chromosomal microarray (CMA) and candidate gene panels, are often employed based on suspected diagnoses. Rapid advancements in next-generation sequencing (NGS) technologies allow for more comprehensive genetic evaluation which is already recommended for patients with ventricular dysfunction, primary arrhythmias, and pulmonary hypertension (PH). Broad application of NGS in intensive care settings for pediatric heart disease has not been extensively investigated. Aims: Evaluate diagnostic efficacy of NGS in critically ill pediatric patients with cardiac disease. Methods: Retrospective cohort of patients who underwent exome or genome sequencing in a pediatric CICU between January 2020 and August 2023. Results: Exome or genome sequencing was performed on 49 patients with median testing age of 46 days (IQR 7-609). Primary cardiac phenotypes included congenital heart disease, ventricular dysfunction, arrhythmia, and PH. Forty-two pathogenic or likely pathogenic variants were identified and 23 (46.9%) resulted in a genetic diagnosis, of those, 16 (69.6%) were associated with a cardiac phenotype. Positivity rate did not differ between primary cardiac phenotypes but was significantly higher when the patient had associated multiple congenital anomalies (Fig. 1). Genome sequencing trended towards a higher positivity rate (54.5%) than exome (31.3%), though did not meet statistical significance (Fig. 1). Notably, 84.6% and 38.5% of the identified pathogenic variants would have remained undetectable by CMA and many commercially available gene panels, respectively. Conclusion: Exome and genome sequencing demonstrate high diagnostic yield across isolated and non-isolated cardiac disease and various cardiac phenotypes with diagnostic efficacy surpassing CMA and many commercial gene panels. As NGS technologies evolve, they promise to streamline diagnoses and enhance therapeutic decision-making for this patient population.
Abstract 4136692: Spatial Transcriptomics Identifies Novel Clinical Markers to Classify the Etiology of Rare and Aggressive Cardiac Sarcomas
Authors: Liwei Zhang, Dan Yuan, Meng Dong, Ying Cai, Su-Han Jin, Benjamin Frey, Udo Gaipl, Pin Sun, Celia Martinez-Jimenez, Jinjing Wang, Hu Ma, Jian-Guo Zhou
Journal: Circulation (2024)

Background: Cardiac sarcomas, such as leiomyosarcoma (LMS), synovial sarcoma (SS), and undifferentiated pleomorphic sarcoma (UPS), lack sufficient diagnostic markers for early diagnosis and tailored therapeutic interventions. Understanding their molecular signatures with spatial-temporal resolution compared to normal heart tissue is crucial. Hypothesis: Spatial transcriptomics will reveal a comprehensive set of novel clinical markers, including changes in cellular composition, stemness, and metabolic profiles unique for each cardiac sarcoma subtypes. Aims: Identify novel molecular markers for the accurate diagnosis of cardiac sarcoma subtypes. Methods: Using 10X Visium spatial transcriptomics, we analyzed three cardiac sarcoma subtypes (LMS, SS, UPS) and compared them with normal heart tissue. Differential expression analysis identified novel target genes suitable for clinical disease stratification. Subsequently, machine learning models reveal an unbiased transcriptomic profile to distinguish normal from sarcoma tissues. Finally, immunohistochemistry analysis validated the differential marker gene expression. Results: We identify several novel clinical markers, such as IGKC, PCOLCE, NET1, TLE2, MDFI, BGN, TNNC1, and CNN3, that classify normal heart tissue from sarcoma subtypes. Machine learning models and immunostaining analysis confirm the transcriptomic signature in each sarcoma subtype. Pathway enrichment analysis show LMS enriched in antigen processing and B cell-mediated immunity, SS in protein folding and response to incorrect proteins, and UPS in axon development and Wnt signaling regulation. Trajectory Reconstruction Analysis indicate higher stemness scores in all sarcomas, with SS highest, followed by UPS and LMS. Additional cell cycling analysis show LMS cells in G2M phase, SS in G1, and UPS in S phase. SS express a high number of cancer stem markers (EZH2, BMI1, KDM5B, LGR5, HIF1A), while UPS express KDM5B and CTNNB1, and LMS show fewer stem-related marker genes (EZH2, BMI1, KDM5B, CTNNB1). Both SS and LMS express CD44. Glucose and oxidative pathways are also differentially regulated in each sarcoma subtype. Conclusion: Spatial transcriptomics uncovers distinct clinical markers, stemness characteristics, and metabolic activity profiles in cardiac sarcomas, offering insights for fast, accurate and improved diagnostics and therapeutics.
Abstract 4136561: Music therapy for postprocedural pain in patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials
Authors: Lucas Barbosa, Beatriz Araujo, Giulia Almiron, Ivo Queiroz, Victor Dante Parriao, Daniela de Oliveira Vieira
Journal: Circulation (2024)

Background: Patients undergoing cardiac surgeries often experience significant levels of pain and anxiety, which can impair effective recovery. Music therapy has been proposed as a non-pharmacological intervention to alleviate these symptoms. This meta-analysis aimed to evaluate the effectiveness of music therapy in patients undergoing cardiac surgeries. Methods: We systematically searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) analyzing music therapy in patients undergoing cardiac surgeries. We pooled mean differences (MD), and standardized mean differences (SMD) for continuous outcomes with 95% confidence intervals (CI) with a random-effects model. We performed a trial sequential analysis (TSA) to assess the random risk of pain, and conducted a subgroup analysis to compare heart and respiratory rate between children and adults. We used R version 4.3.2 and TSA version 0.9.5.10 for statistical analyses. Results: Our meta-analysis included 20 RCTs comprising 1379 patients, of whom 715 (51.9%) were randomized to music therapy. Compared with control, music significantly reduced postoperative pain (SMD -0.59; 95% CI: -0.76 to -0.41; p&lt;0.05; Figure A), and anxiety (SMD -0.59; 95% CI: -0.74 to -0.44; p&lt;0.05; Figure B). There was a significant difference between groups in heart rate (MD -5.68 bpm; 95% CI: -9.73 to -1.63; p&lt;0.05), overall there was an important subgroup interaction between children and adults (p=0.01). In children, music therapy reduced the respiratory rate (MD -5.98 ipm; 95% CI: -6.71 to -5.25) compared to control, whereas in adults, no significant differences were observed among these groups, overall, there was a significant subgroup interaction (p&lt;0.01). For the primary endpoint, TSA suggested a low risk of type 1 error, therefore these results may be conclusive. Conclusion: In patients undergoing cardiac surgery, music therapy reduced postoperative pain, anxiety, heart rate, and respiratory rate.
Abstract 4135872: Effects of In-vivo Contact Force on Pulsed Field Ablation Lesion Size in Porcine Ventricles
Authors: Taro Koya, Naoto Otsuka, Jason Tri, yang ying, Samuel Asirvatham, Duy Nguyen
Journal: Circulation (2024)

Background: Pulsed field ablation (PFA) is an innovative modality for treating arrhythmias that is mostly non-thermal and renders myocardial tissue non-viable by creating pores in cardiac cell membranes. The impact of contact force (CF) on PFA efficacy is not well characterized. Hypothesis: We hypothesize that, while contact is necessary for PFA, increasing CF will not have a significant effect on in vivo ablation lesion size. Aim: We seek to investigate the effects of CF on acute PFA lesions in a beating porcine heart model. Methods: The ventricles of 7 porcine animals were ablated in vivo with PFA (500V, at 20μs for 50 pulses separated by 200ms) using a focal bipolar irrigated ablation catheter and BTX 830 electroporation generator (Harvard Apparatus). CF was measured before and after each PFA application using CARTO 3. Lesions were divided into standard CF (5-15g), high CF (16-30g), and very high CF (&gt;31g). Results: A total of 46 lesions were analyzed. Gross pathology showed no significant difference in maximum width, lesion depth, and lesion volume between the three groups ( Figure 1A-B ). Linear regression showed a decrease of 0.003 mm in depth (depth = -0.003 × CF + 1.8, R = 0.05), an increase of 0.01 mm in width (width = 0.01 × CF + 5.7, R = 0.09), and a decrease of 0.05 mm 3 in volume (volume = -0.05 × CF + 26.8, R = 0.03) for each additional gram of CF ( Figure 1C ). Conclusion: While contact is necessary, increasing CF did not have a significant effect on in-vivo PFA lesion dimensions in a beating porcine heart model.
Abstract 4136358: Diagnostic accuracy of Apple Watch Electrocardiogram for Atrial Fibrillation: A Systematic Review and Meta-Analysis
Authors: Sufyan Shahid, Minahil Iqbal, Humza Saeed, Sara Hira, Amna Batool, Aman Goyal
Journal: Circulation (2024)

Background: Electrocardiography (ECG) stands as the gold standard for the evaluation of cardiac arrhythmias. Recent smartwatches aim to promptly detect rhythm abnormalities enhancing user experience. However, the accuracy of these devices remains controversial. Our purpose was to perform a systematic review and meta-analysis evaluating the diagnostic performance of the Apple Watch electrocardiogram in detecting atrial fibrillation (AF). Methods: The literature search was conducted on PubMed, Embase, and Cochrane through April, 2024 for studies comparing the diagnostic accuracy of Apple Watch to standard 12 Lead ECG. Statistical analysis was performed using R Software version 4.4.0. Pooled analyses of sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were determined along with their 95% confidence intervals (CI). The quality of studies was analyzed using the QUADAS-2 tool. Results: The meta-analysis included 11 studies comprising 13,490 participants. Their mean age was 62.56 ± 3.92 years and 28% of the population were females. The pooled sensitivity and specificity of Apple Watch for detecting AF was 94.8% (95% CI 91.7 - 96.8%) and 95% (95% CI 88.6 - 97.8%) respectively. The AUC was 0.96 (95% CI 0.92 - 0.97; Figure 1). Sensitivity analysis for heterogeneity revealed no significant change in values for sensitivity 94.8% (95% CI 91.7-96.8%) and specificity 94.9% (95% CI 88.6-97.8%). The studies had a low risk of bias in Index test and reference standard domains, but a high risk of bias in patient selection and Flow and timing domains. Conclusion: The Apple Watch ECG shows a high accuracy in detecting atrial fibrillation, providing a convenient and timely option for such patients.
Abstract 4136785: Interpreting Population Mean Treatment Effects in the Kansas City Cardiomyopathy Questionnaire
Authors: Mohammad Abdel Jawad, Philip Jones, Suzanne Arnold, David Cohen, Charles Sherrod, Mirza Khan, Nobuhiro Ikemura, Paul Chan, John Spertus
Journal: Circulation (2024)

Introduction: The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a common outcome in heart failure trials. While comparing means between treatment groups improves statistical power, mean effects do not necessarily reflect the clinical benefit experienced by patients. Objectives: To evaluate the relationship between mean KCCQ treatment effects in clinical trials and the proportions of patients experiencing clinically important improvements across a range of heart failure etiologies and interventions. Methods: We performed a patient-level meta-analysis of 11 randomized trials (9,977 patients) to examine the relationship between mean KCCQ Overall Summary Score (OSS) treatment effects and the absolute differences in the proportions of patients experiencing clinically important (≥5 points) and moderate or larger (≥10 points) improvements. Validation was performed in 7 additional trials. Results: Group mean KCCQ-OSS differences were strongly correlated with absolute differences in clinically important changes (Spearman correlations 0.76-0.92). For example, a mean KCCQ-OSS treatment effect of 2.5 points (half of a minimally important difference for an individual patient) was associated with an absolute difference of 6.0% (95% prediction interval [PI] 4.0-8.1) in the proportion of patients improving ≥5 points and 5.0% (95% PI 3.1-7.0) in the proportion improving ≥10 points, corresponding to NNTs of 17 (95% PI 12-25) and 20 (95% PI 14-33), respectively. Similar relationships were observed in the validation studies. Conclusions: Inferences on clinical impact based on population-level mean treatment effects are misleading since even small between group differences may reflect clinically important treatment benefits at the patient level. Clinical trials should explicitly describe the distributions of patient-level KCCQ changes to support clinical interpretation of their results.
Abstract 4136509: Children in Foster Care with Heart Disease Have Greater Resource Utilization and Mortality
Authors: Anna Martens, Kimberlee Gauvreau, Taylor Smith, Michael Laccavole, Jennifer Perez, Joanne Cox, Richard Antonelli, Snehal Shah, Jane Newburger, Katie Moynihan
Journal: Circulation (2024)

Background: While children and youth in foster care (CYFC) have greater healthcare needs generally, data are lacking in heart disease. We characterize CYFC with heart disease, assess the impacts of being in foster care on outcomes, and examine validity of ICD-10 code Z62.21 for identification of CYFC in administrative data. Methods: In this single-center, retrospective cohort study of all cardiac surgical patients (&lt;18yo) admitted 2017-2022, CYFC were identified using institutional Electronic Medical Records via natural language processing or ICD codes, with confirmation by chart review. Demographics, medical characteristics and outcomes of CYFC were compared to children not in foster care. Generalized linear models assessed associations with primary outcomes of mortality at current follow-up (logit link) and total hospital days (log link), controlling for clinical factors and length of follow-up. We separately added Child Opportunity Index (COI) and payer to models. This cohort was then studied in the administrative pediatric health information system (PHIS) dataset to calculate ICD code sensitivity and specificity. Results: Of 4,431 cardiac surgical patients, 67 (1.5%) were in foster care. CYFC did not have significantly higher mortality (9% vs 5.8%), 30-day readmission or cardiac reoperation, number of complex chronic conditions (CCC), RACHS-2, or distance from center compared to non-CYFC. CYFC had lower COI (median 61 vs 72, p=0.016) and more Medicaid coverage (87% vs 40%, p&lt;0.001). Length of stay after index surgery was similar; however, cumulative hospital days during the study were significantly higher for CYFC (median 22 [IQR 10,45] vs 12 [6,27], p&lt;0.001). Adjusting for RACHS-2, CCC, age, readmission, reoperation, and follow-up duration, CYFC had higher odds of mortality (2.7 [95%CI 1.0,6.9] p=0.046) and more total hospital days (p=0.008). With COI or payer in the model, CYFC was not associated with mortality but remained an independent risk factor for more total hospital days. Only 16/67 (23.9%) of CYFC were coded with the Z62.21 in PHIS, yielding sensitivity of 21.9% (95%CI 13.1,33.1), and specificity of 100% (99.9,100). Conclusion: CYFC with heart disease have a relative social disadvantage, greater hospital resource utilization, and long-term mortality despite similar illness severity. Improved capture of foster care status in administrative data is needed to guide future studies and reduce health disparities for the vulnerable population of CYFC.
Abstract 4136581: Shared Genetic Burden of Ischemic and Non-Ischemic Dilated Cardiomyopathy
Authors: Louie Cao, Joshua Rushakoff, Zijun Zhang, Ian Williamson, Anja Karlstaedt, Michelle Kittleson, Lawrence Czer, Evan Kransdorf
Journal: Circulation (2024)

Introduction: Ischemic dilated cardiomyopathy (IDCM) is defined as DCM caused by severe stenosis of one or more coronary arteries. Patients with non-ischemic dilated cardiomyopathy (NIDCM) have normal coronary arteries and may possess rare disease-causing variants in cardiac proteins such as TTN . However, IDCM and NIDCM share echocardiographic and pathologic features, possibly suggesting a shared etiology. Hypothesis: There is a similar prevalence of pathogenic (P)/likely pathogenic (LP) variants in patients with IDCM compared to patients with NIDCM. Aims: We compared the prevalence of P/LP genetic variants in DCM-associated genes in a cohort of patients with NIDCM or IDCM who received a heart transplant. Methods: We conducted a retrospective cohort study of patients who received a heart transplant between May 2017 and October 2023 at Cedars Sinai Medical Center in Los Angeles, CA. All subjects had LVEF ≤ 50% and LVEDD ≥ 95 th percentile for sex and height. Whole exome sequencing was performed on explanted heart tissue. We assessed for rare variants (minor allele frequency &lt;0.1%) in genes with a definite, strong, or moderate rating in the ClinGen DCM Gene Curation Expert Panel. Variant pathogenicity was interpreted using the American College of Genetics and Genomics criteria for DCM. Ischemic cardiomyopathy was defined by the Felker criteria (Felker et al., JACC 2002). Results: We included 60 subjects: 16 with IDCM and 44 with NIDCM. There was no difference in LVEF or LVEDD between groups (TABLE). 2/16 (12.5%) patients with IDCM carried a P/LP variant, both of which were in TTN . 11/44 (25.0%) patients with NIDCM carried a P/LP variant: 6 in TTN and 1 each in FLNC, ILK, LMNA, MYH7 , and RBM20 . The prevalence of TTN variants in each group was similar (12.5% in IDCM vs. 13.6% in NIDCM) and higher than the expected frequency in the general population (0.2%). There was no significant difference in the prevalence of P/LP variants between the groups (chi-squared p-value 0.493, Bayes factor 0.45). Conclusion: Patients with IDCM exhibited a similar prevalence of P/LP variants to NIDCM patients, which suggests a shared genetic burden. If further studies confirm our findings, genetic testing for individuals with IDCM may be warranted.
Abstract 4135893: The Importance of Genetic Testing in Diagnosis and Management of Peripartum Cardiomyopathy: A Case Study
Authors: Zoee D'Costa, Eugene Wong, Min Zhang, Gregory Fishbein, Jessica Wang, Megan Kamath, Negeen Shahandeh
Journal: Circulation (2024)

Introduction: At least 15% of women diagnosed with peripartum cardiomyopathy (PPCM) are found to have a pathogenic genetic variant associated with dilated cardiomyopathy. We present a patient with PPCM who required orthotopic heart transplantation (OHT) for cardiogenic shock. Her explant pathology and genetic testing played a critical role in identifying the etiology of her cardiomyopathy. Case Description: A 22-year-old primigravid woman with a history of asthma presented in labor and underwent a Cesarean delivery for non-reassuring fetal heart tones. She had noted exertional dyspnea, a dry cough, and orthopnea in her final weeks of pregnancy but had an otherwise uncomplicated pregnancy. Immediately following delivery, she suffered a cardiac arrest with pulseless electrical activity and developed cardiogenic shock. She was found to have severe biventricular systolic dysfunction with a left ventricular (LV) ejection fraction of 10%. She was cannulated on veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and transferred to our center. She was transitioned from VA-ECMO to an axillary Impella 5.5 device but continued to require inotropic support without evidence of LV recovery. Therefore, she was listed for and successfully underwent OHT. Explant pathology (Figure 1) revealed arrhythmogenic cardiomyopathy (ACM). Her family history was significant for a maternal grandfather who died of an unspecified arrhythmia at age 57. Genetic testing via a commercial arrhythmia and cardiomyopathy panel revealed a pathogenic desmoplakin ( DSP) truncating variant ( DSP tv) p.Ser1894Leufs*34 in the N-terminal constitutive NMD-competent region, confirming the diagnosis of ACM. The patient had minor cutaneous findings, including curly hair, consistent with the clinical presentation of DSP -mediated ACM. Discussion: This case highlights the importance of genetic testing in all patients with PPCM, as well as attention to the explant pathology in those who undergo OHT. These practices can elucidate the mechanism of cardiomyopathy, inform the risks of disease progression and of relapse with subsequent pregnancy, and allow for cascade testing of family members.
Abstract 4136724: Early Adoption of Sodium-Glucose Cotransporter-2 Inhibitor Among Patients Hospitalized with Heart Failure and Preserved Ejection Fraction in the United States
Authors: Mohammad Abdel Jawad, John Spertus, Stephen Greene, Uchechukwu Ikeaba, Karen Chiswell, Gregg Fonarow, Paul Chan
Journal: Circulation (2024)

Introduction: In August 2021, the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction (EMPEROR-Preserved) found that empagliflozin reduced rates of cardiovascular death and hospitalization by 21% in patients with heart failure with mildly reduced ejection fraction of 41-49% (HFmrEF) and with preserved ejection fraction of &gt; 50% (HFpEF). National trends in Sodium-Glucose Cotransporter-2 Inhibitors ( SGLT2i) use among patients with HFmrEF and HFpEF following this trial are unknown. Methods: We identified patients hospitalized for HFmrEF and HFpEF in the AHA Get With The Guidelines-Heart Failure registry between July 2021 and September 2023. We examined temporal trends in SGLT2i prescriptions at discharge after the publication of the EMPEROR-Preserved trial using the Cochran-Armitage trend test. Results: Among 158,849 hospitalizations with an EF &gt; 40% across 557 hospitals, 27,712 (17.4%) had HFmrEF, and 131,137 (82.6%) had HFpEF. Overall, 22,126 (13.9%) patients were discharged with a prescription for SGLT2i, with higher rates among those with HFmrEF (18.5% vs. 13.0% in those with HFpEF). Patients prescribed SGLT2i were more likely to be younger, male, of Black race, have type II diabetes, have Medicaid insurance, and be discharged from large hospitals. After publication of the EMPEROR-Preserved trial during Q3 2021, rates of SGLT2i prescription at hospital discharge increased from 4.2% in Q3 2021 to 23.5% in Q3 2023, with a 29% relative increase in the rate of SGLT2i prescription for each quarter (adjusted OR, 1.29 [95% CI: 1.28, 1.29]; P&lt;.001). Prescription rates increased from 6.1% in Q3 2021 to 31.6% in Q3 2023 among patients with HFmrEF and from 3.8% to 21.9% for patients with HFpEF (Figure). Conclusion: In the U.S., the use of SGLT2i at discharge has increased for patients hospitalized with HFmrEF and HFpEF following the publication of the EMPEROR-Preserved trial. However, the majority of eligible patients hospitalized for decompensated HF remain untreated with SGLT2i, indicating the need for further efforts to apply the scientific findings into clinical practice.