tbuckley/cabot-search huggingface dataset:
Abstract 4148073: Expect the Unexpected: Type A Aortic Dissection in Pregnant Patient with Marfan Syndrome
Authors: Lauren Stucky, Saurabh Rajpal, Lauren Lastinger
Journal: Circulation (2024)

Case Description: A 26 yo woman with Marfan Syndrome (MFS, FBN1 ), ectopia lentis, aortic dilation and no family history of MFS or aortic dissection was evaluated for preconception counseling. She was asymptomatic, and the size of her aortic root (~4cm) and ascending aorta (~3.5cm) had been stable for over 5 years. She was counseled that risk of cardiac events during her pregnancy is high, but lower compared to those with aortic sizes &gt;4.5cm. Once pregnant, she was followed closely with imaging every trimester (MRA at 25 weeks gestation showed stable aortic sizes). Cardio-obstetric recommendations included: CARPREG II score: 2, mWHO class: III, consideration of assisted second stage due to aortic root dilation. She was counseled on symptoms of aortic dissection and to seek emergency care should those symptoms arise. At 27 weeks gestation, she presented to the ED with intense chest and neck pain, shortness of breath, and headache. Emergent CT showed aortic root (4.1cm) and proximal ascending aortic dissection with propagation into the left main coronary artery (Figure 1). She underwent emergent C-section followed by aortic root and ascending aorta replacement and mechanical aortic valve replacement due to severe regurgitation. She was discharged in stable condition 8 days after an uncomplicated post-operative recovery. Her baby is recovering in the NICU. Discussion: While risk of aortic dissection in women with MFS is higher during pregnancy, recent studies suggest relative safety with aortic root diameters up to 4.5cm. Our case highlights that even at “lower risk” aortic sizes, aortic dissection remains an important risk for such women. Educating patients and providers about the acute symptoms of aortic dissection and forming an action plan for timely intervention can be lifesaving. Furthermore, some genetic mutations (e.g. TGBR1/2 or SMAD3 ) and sequence variants within the FBN1 gene may pose a higher risk of aortic dissection at smaller aortic diameters. Our patient’s pathogenic FBN1 mutation (-c.2114-5T&gt;G, previously classified as a VUS) highlights the importance of genetic testing: prophylactic surgery at sizes &lt;4.5cm may be considered with high-risk genetic variants or a family history of aortic dissection.
Abstract 4140108: A CRISPR-Activation CROP-seq Screen Identifies HMGN1 as a Dosage-Sensitive Regulator of Heart Defects in Down Syndrome
Authors: Sanjeev Ranade, Feiya Li, Sean Whalen, Pelonero Angelo, Lin Ye, Yu Huang, Abigail Brand, Tomohiro Nishino, Mauro Costa, Rahul Mital, Ryan Boileau, Frances Koback, Arun Padmanabhan, Alexander Merriman, Langley Wallace, Annie Nguyen, Nikolaus Poulis, Casey Gifford, Katherine Pollard, Deepak Srivastava
Journal: Circulation (2024)

Introduction/Background: Congenital heart defects (CHD) are the most common form of developmental abnormalities, occurring in ~1% of live births, and can arise due to altered dosage of genes essential for cardiogenesis. Aneuploidy accounts for nearly 15% of CHD and the most frequent form involves trisomy of chromosome 21 (Ch21), resulting in Down Syndrome (DS). CHD is present in ~50% of DS cases, with a 1000-fold enrichment of atrioventricular canal (AVC) defects that disrupt the junction of the atria and ventricles. Hypothesis: We hypothesize that the presence of a third copy of one or more genes on Ch21 underlies AVC and other cardiac defects; however, the dosage-sensitive CHD gene(s) on Ch21 causing this are not fully defined. Methods: We used human pluripotent stem cells derived from an individual mosaic for DS, allowing us to compare Ch21 trisomy cells with isogenic control cells disomic for Ch21. We performed single cell RNA-sequencing (scRNA-seq) to define the transcriptional dysregulation associated with DS in atrioventricular canal myocardial cells (AVCM). We then introduced a CRISPR-activation transgene to disomic cells and delivered small guide RNAs (sgRNAs) against 66 candidate Ch21 CHD genes. We developed a new machine learning algorithm to assign a trisomic score to CRISPR perturbed (CROP-seq) cells. Finally, we reduced the copy number of our top candidate gene in a mouse model of Down Syndrome and used microCT to assess incidence of cardiac septal defects. Results: Using human pluripotent stem cell and mouse models of DS, we identify HMGN1, a nucleosome-binding epigenetic factor on Ch21, as a dosage-sensitive regulator of cardiac defects in DS. Single cell transcriptomics revealed that human AVC cardiomyocytes shifted to a more ventricular myocardial state in trisomy 21 hiPS-derived cells. CRISPR-activation in isogenic disomic cells of 66 candidate Ch21 genes expressed in heart development, followed by single cell RNA-sequencing (CROP-seq) combined with machine learning predictions indicated that increased expression levels of HMGN1 altered the transcriptional state of atrioventricular cardiomyocytes similar to trisomy 21. Finally, reduction of Hmgn1 from three to two alleles in a mouse model of DS attenuated the incidence of cardiac septal defects. Conclusion: Our results identify HMGN1 as a dosage sensitive regulator of heart defects in DS and represent a generalizable approach for identifying candidate genes within areas of aneuploidy.
Abstract 4122307: Longitudinal Changes in Parent-reported Quality of Life in Children with Single Ventricle
Authors: Karen Uzark, Sunkyung Yu, Katherine Afton, Andrew Atz, Alejandro Floh, Nadine Kasparian, Linda Lambert, Tonia Morrison, Victoria Pemberton, Amee Shah, Erica Sood, Divya Suthar, Felicia Trachtenberg, Jodie Votava-Smith, Jason Williams, Jane Newburger, Caren Goldberg
Journal: Circulation (2024)

Introduction: Increased knowledge of quality of life (QOL) and the potential impact of the Fontan on QOL is essential to improving outcomes in patients with single ventricle. The primary aim of the Pediatric Heart Network Single Ventricle Reconstruction (SVR) trial II was to investigate outcomes in subjects with SV at age 6 yrs while SVR III characterized outcomes in this cohort at age 10-12 yrs. Aims: The purpose of this study was to evaluate changes in health-related QOL from SVR II to SVR III and to identify factors associated with changes in QOL over time. Methods: Parents completed proxy-reports for their child using the Pediatric Quality of Life Inventory (PedsQL) generic and cardiac scales at SVR II and SVR III. Within-subject differences in PedsQL scores and proportions scoring in the ‘at-risk’ range for significantly impaired QOL between time points were examined using one-sample t-test and McNemar’s tests, respectively. Factors associated with changes in QOL were evaluated using standard univariate tests. Results: A total of 163 patients were included (63% male, 89% Caucasian, 16% Hispanic). PedsQL scores reported by parents decreased across all domains: total score -6.1 ± 17.1, p &lt;.0001; physical -4.0 ± 22.3, p=0.02; psychosocial -7.2 ± 17.4, p&lt;.0001; emotional -6.5 ± 20.7, p=.0001; social -6.6 ± 22.6, p= 0.0003; and school -8.6 ± 22.5, p&lt;.0001, functioning. No significant change in parent-reported heart problems/cardiac symptoms was detected across timepoints (-1.0 ± 20.4, p=0.52). Proportions with impaired QOL increased over time: total 28 to 39%, p=.01, physical 27 to 39%, p=.01, psychosocial 25 to 40%, p=.002, emotional 20 to 34%, p=.001, social 22 to 31%, p=.06, and school 21 to 38%, p=.0001. Only treatment for a psychological or behavioral disorder (n=26) was significantly associated with decline in psychosocial (mean -14.0 vs. -5.9; p=.03) and emotional (mean -17.1 vs. -4.5; p=.004) functioning scores. There was no significant association between socioeconomic status, Vineland adaptive scores at SVR II, or interval complications or procedures and changes in QOL. Conclusion: As perceived by their parents, health-related QOL in children with SV decreases over time unrelated to cardiac symptoms and complications. The greatest decline was in school functioning with 1 in 3 children having significantly impaired school QOL at SVR III. Greater attention to assessment of learning and psychosocial needs is essential to improve QOL in patients with SV.
Abstract 4135624: A Hypertrophic Cardiomyopathy Polygenic Score Modifies Penetrance of Pathogenic Hypertrophic and Dilated Cardiomyopathy Variants in Opposite Directions
Authors: Sarah Abramowitz, Lily Hoffman-Andrews, John Depaolo, Renae Judy, Anjali Owens, Scott Damrauer, Michael Levin
Journal: Circulation (2024)

Background: Hypertrophic (HCM) and dilated (DCM) cardiomyopathy have been postulated to represent morphologically opposing cardiac disease traits, with genetic pathways implicated in HCM demonstrating inverse relationships with DCM. The degree to which polygenic risk for HCM protects from DCM in individuals at genetic risk of DCM remains unexplored. Research Question: Is polygenic risk for HCM protective against developing DCM in carriers of titin truncating variants? Methods: Associations between polygenic risk for HCM, monogenic variants, and cardiomyopathy outcomes were modeled among Penn Medicine BioBank (PMBB) participants genetically similar to European reference populations using logistic regression. Polygenic risk for HCM was determined using a previously published HCM polygenic score (PGS; PGS Catalog PGS000739; Harper et al. 2021); scores were PCA adjusted, and the mean and variance were normalized using pgsc_calc. Pathogenic variants in definitive HCM genes were identified using ACMG criteria. Titin truncating variants in high percentage spliced in exons (TTNtv) were considered pathogenic. HCM and DCM outcomes were assigned based on diagnosis codes +/- clinical notes in the electronic health record. Results: Of 26,728 PMBB participants, 205 (0.77%) had HCM and 589 (2.2%) had DCM. 289 had a TTNtv, and 144 had a pathogenic HCM variant. Pathogenic HCM variant status (n=144) conferred a 76-fold increase in HCM risk (p=1.8 e-87). A one standard deviation change in HCM PGS had a significant positive association with HCM (OR 1.6; p=1.5e-9) and negative association with DCM (OR 0.72; p=1.e-12). TTNtv status (n=289) was associated with an increased risk of DCM (OR 5.0; p=1.4e-12). An interaction term between TTNtv status and HCM PGS had a negative association with DCM (OR 0.61; p=4.5e-2). Among the top HCM PGS quintile, there was no statistically significant difference in DCM risk between those with and without TTNtv (Figure 1). Conclusions: These results provide additional evidence that HCM and DCM are influenced by polygenic background. We observe that polygenic risk of HCM additively increases risk of HCM among pathogenic HCM variant carriers and may synergistically protect from DCM among TTNtv carriers.
Abstract 4147610: Efficacy and Safety of Selective Cardiac Myosin Inhibitors in Symptomatic Hypertrophic Obstructive Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials
Authors: Hitesh Bhatia, Muhammad Khan, Adishwar Rao, Akriti Agrawal, Siddharth Agrawal, . Parul, Rakendu Jayasree Rajendran, Shraddha Bhattarai, Asna Aafreen, Saurabh Sharma
Journal: Circulation (2024)

Background: Hypertrophic Obstructive Cardiomyopathy (HOCM) is an autosomal dominant inherited condition with limited management options, primarily focusing on symptom improvement through beta blockers. A novel selective cardiac myosin inhibitor, Mavacamten has been shown to improve exercise tolerance and NYHA functional class as compared to placebo in multiple randomized controlled trials (RCTs). A recent RCT from 2024 studied another oral cardiac myosin inhibitor, Aficamten which potentially decreases left ventricular outflow tract obstruction (LVOTO) in symptomatic HOCM. One limitation of all these RCTs, for obvious reasons, is the small sample size, which poses a challenge in its actual clinical significance. Aims: To analyze the efficacy and safety of novel selective cardiac myosin inhibitors in symptomatic HOCM patients Methods: We included 4 RCTs, comparing the efficacy and safety of selective cardiac myosin inhibitors and placebo groups. These studies were selected through a detailed search of the MEDLINE, COCHRANE, and PUBMED databases. We compared various common primary and secondary endpoints between both the groups: changes in exercise tolerance, NYHA functional class, and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS). The results were reported as Odds Ratios (OR) with 95% confidence intervals (CI), using a random effects model. Results: The outcomes from 704 HOCM patients, which consisted of 361 patients who received a myosin inhibitor and 343 who received a placebo were analyzed. The primary endpoint in all the studies was improvement in exercise tolerance [measured as 1.5 mL/kg per min or greater increase in peak oxygen consumption (pVO2)], which was not statistically significant in our study (OR: 1.75, 95% CI: 0.89-3.43, p:0.1). There was a statistically significant improvement in ≥1 NYHA functional Class (OR: 3.9, 95% CI:2.49-6.12 p&lt;0.05). There was no significant change seen in KCCQ-CSS (OR: 1.26, 95% CI: 0.75-2.12, p:0.3) and1 or more Serious Adverse Events (OR: 0.75, 95% CI: 0.42-1.32, p:0.3). (Figures A-D) Conclusion: Novel cardiac myosin inhibitors have shown statistically significant results in improving NYHA functional class, but not much difference in objective criteria like pVO2 with no significant adverse events. While these results appear promising and 2024 ACC/AHA guidelines have Class 1 Recommendation regarding their use for symptomatic HOCM, further analysis from a large population is needed.
Abstract Sa1106: Computed Tomography Imaging After In-Hospital Cardiac Arrest: An Observational Cohort Study
Authors: Jack Galfund, Martin Hoang, Alban Cela, Ashley Miller, Lewis Eisen, Michelle Gong, Ari Moskowitz, Luke Andrea
Journal: Circulation (2024)

Introduction/Background: Computed tomography (CT) imaging is a promising method for diagnosing patients after return of spontaneous circulation (ROSC) from cardiac arrest. CT information could alter management, improving patient outcomes. There are data supporting use after out-of-hospital arrests, but use and impact of CT imaging after in-hospital-cardiac arrest (IHCA) has not been investigated. Research Question/Hypothesis: We hypothesize that CT imaging will identify acute pathology, resulting in a change in management. Goals/Aims: Our aim is to describe the rates of use, findings, and consequences of CT imaging after IHCA. Methods/Approach: We screened for the first IHCA on admission between 1/26 2023, and 1/302024 at 3 hospitals. Patients 18 years of age or older who achieved ROSC were included. Information was collected on demographics, type of imaging performed, imaging findings, and whether the findings acutely changed management. A change in management was defined as a subsequent change in medications, procedures, or consultations that would not have otherwise occurred and was specifically performed to reverse, mitigate, or treat the imaging finding, based on review of chart documentation by critical care fellows and medicine residents. Results are reported as counts and percentages. Results: We screened 638 IHCA at 3 hospitals. Of the 201 patients meeting inclusion criteria, 72 (35.8%) died within 24 hours after ROSC. Of those who survived 24 hours, 58 of 129 (45.0%) received CT imaging in the 48 hours after ROSC, 53 (41.1%) received a head CT, 26 (20.2%) received a chest CT, 19 (14.7%) received an abdomen/pelvis CT, and 4 (3.1%) received a CT that was not head, chest, or abdomen/pelvis. The most common findings were ischemic stroke (15), pulmonary airspace opacities (23), and pleural effusion (15). An acute finding (previously unknown) was identified in 32 of 58 scans (55.2%), and there was an acute change in management because of the acute finding in 21 (65.6%) of those patients. For 8 patients (13.8%), the scan identified an acute finding thought to have contributed to the cardiac arrest. Of the 58 patients who received CT imaging, 2 of them (3.4%) suffered cardiac arrest while receiving the CT scan. Conclusions: CT imaging within 48 hours after IHCA frequently identified acute pathology, resulting in a change in management. Complications were seen, although we do not know if these were a result of the CT imaging, related transportation, or other causes.
Abstract 4136975: Lipoprotein (a) Discovery Project: Assessing Patient and Professional Education Needs
Authors: Meg Yuan, Allison Groom, Eliana Collins, David Pena, Kristin Colson, Jeremy Skinner, Michelle Congdon, Alyssa Pressley
Journal: Circulation (2024)

Introduction: It is estimated that 1 in 5 Americans have high lipoprotein (a) [Lp(a)] levels. High levels of Lp(a) are an independent, predominantly inherited, and causal risk factor for atherosclerotic cardiovascular disease (ASCVD). More investigation is needed to better understand the gaps in both professional and patient education on Lp(a) and its associated risk with ASCVD. Goals: The American Heart Association (AHA) is implementing a national 3-year initiative called the Lp(a) Discovery Project to understand system-level practice patterns for patients screened for high Lp(a) and develop models for national education. We aim to gauge an understanding of healthcare professional (HCP) and patient awareness, perceptions, knowledge, and behaviors of Lp(a) to develop a comprehensive educational approach that ultimately encourages patient-provider shared decision-making. Methods: To assess patient education needs, an online survey was conducted from October 11 to November 6, 2023, by Harris Insights&amp;Analytics LLC with a nationally representative sample of 3,006 U.S. adults 18 years+. To assess professional education needs, the AHA engaged 10 champions from diverse health systems with established Lp(a) screening processes and workflows to participate in a Learning Healthcare System model to share best practices, inform on models for Lp(a) screening, and provide input on professional education topics. Results: The patient survey revealed that 34% of adults do not perceive high Lp(a) to pose an increased risk of heart attack, peripheral artery disease or stroke. If told that high Lp(a) does increase this risk, 63% are motivated to have their Lp(a) level checked and 88% would be motivated to reduce their risk for these conditions if they had high Lp(a). Ultimately, HCP recommendation was the most significant driver in getting screened among those who had their Lp(a) measured (61%). AHA-led champion interviews revealed that primary and specialty care HCPs need education on the importance of Lp(a) testing and cascade screening for family members as well as care considerations for patients with high Lp(a). Conclusion: Given that patients are most likely to be screened for Lp(a) if their HCP recommends it, we will focus on 1) educating patients and HCPs on the connection between Lp(a) and risk for cardiovascular disease and stroke and 2) providing HCPs with guidance on care considerations for those with high Lp(a) including cascade screening.
Abstract 4124974: Small delays in door-to-balloon time for patients presenting with STEMI do not impact mortality: a quasi-experimental study
Authors: Andrew Oseran, Zaid Almarzooq, Jennifer Rymer, Leo Brothers, Daniel Wojdyla, Lisa Kaltenbach, Robert Yeh
Journal: Circulation (2024)

Introduction: Observational studies have consistently demonstrated a strong association between longer door-to-balloon (DTB) times and increased mortality in patients presenting with ST-elevation myocardial infarction (STEMI). However, the extent to which this association is attributable to unmeasured differences between patients with different DTB times (i.e., confounding), as opposed to a causal impact of longer DTBs is unclear. Aim: In this study, we exploit a natural experiment using an instrumental variable (IV) approach based on weekday vs weekend presentation to evaluate whether incremental delays in DTB times have a causal effect on patient outcomes. Methods: We performed a retrospective analysis of patients undergoing immediate percutaneous coronary intervention (PCI) for STEMI in the CathPCI Registry from 1/2010 to 12/2021 at 1,422 sites. Time of presentation with STEMI (weekday daytime vs weekend daytime) was used as an IV to address potential confounding. A 2-stage IV analysis was used. In-hospital all-cause mortality was the primary outcome. Results: A total of 447,355 patients presented with STEMI during the study period. The average difference in weekend (N=125,787) minus weekday (N=321,568) daytime DTB times was 10.5 minutes. Patient, procedural, and hospital characteristics were well balanced between groups. Overall, in-hospital mortality was 3.5%. In the IV analysis, delays in DTB time were not associated with increased odds of in-hospital mortality (OR 0.99, 95% CI 0.95 to 1.03, P = 0.70). This null association was also observed when limited to hospitals with larger differences (19.5 minutes) between weekend and weekday DTB time (OR 1.00, 95% CI 0.96 to 1.03, P = 0.85) and among patients predicted to have the longest (mean 70.8 minutes) DTB times (OR 1.00, 95% CI 0.94 to 1.07, P = 0.96). Conclusions: Contrary to prior findings, incremental delays in DTB time for patients presenting with STEMI are not associated with increased in-hospital mortality when analyzed using quasi-experimental methods less likely to be influenced by unmeasured confounding. Efforts to further reduce DTB times in patients presenting to hospitals with STEMI are unlikely to improve outcomes. In the current era, policies intended to incentivize better care for STEMI patients should prioritize other measures of quality beyond DTB.
Abstract 4147609: Hypoalbuminemia as predictor of poor functional status in hospitalized patients with advanced heart failure
Authors: Galen Ogg, Juan Cedeno, Matthew Atienza, Paul Ippolito, Akhil Chandra, Vidish Pandya, Patricia Chavez, Serife Eti
Journal: Circulation (2024)

Introduction: Timely involvement of palliative care services for patients with advanced heart failure (HF) improves symptom burden, functional status, and resource utilization. The Karnofsky Performance Scale (KPS) is an objective tool used by palliative care specialists to assess physical ability and guide palliative interventions. Patients with lower KPS have poor outcomes, however evidence linking clinical parameters such as New York Heart Association (NYHA) class, ejection fraction (EF), and albumin with KPS remains limited. Goals: To identify clinical parameters associated with poor functional status in hospitalized patients with advanced HF Methods: Individuals with acute decompensated HF admitted between 2021-2023, ineligible for advanced cardiac therapies, and referred to palliative care were included. Data collected encompassed demographic variables, clinical parameters (NYHA classification, KPS, comorbidities, EF, Brain natriuretic peptide (BNP), albumin, creatinine), and palliative care interventions (family meetings, advanced care planning discussions). Bivariate and multivariate analyses, utilizing Kruskal-Wallis and chi-square tests along with adjusted regression models, were conducted using R to compare characteristics, with a low KPS (≤40) as the primary outcome. Results: A total of 97 individuals were included, with a mean age of 68 ± 17.7 years, 32 (33.0%) were female. Hypoalbuminemia was directly associated with KPS. Patients with albumin levels ≤3 g/dL were more likely to have KPS ≤40 (OR 2.6 [CI 1.03-6.7], p=0.04). NYHA class, EF, serum creatinine, and comorbid conditions (chronic kidney disease, stroke, chronic obstructive pulmonary disease, dementia) were not significantly associated with KPS. Those with lower KPS scores had higher utilization of palliative care services for family meetings, although did not differ significantly in advanced care planning status. Conclusions: In our analysis of hospitalized patients with advanced HF, hypoalbuminemia had the highest predictive value for low functional status. Low KPS score was associated with increased utilization of palliative care services and higher rates of inpatient mortality.