tbuckley/cabot-search huggingface dataset:
Abstract 4118882: Decompensated Heart Failure Secondary to a Non-Coronary Sinus of Valsalva to Right Atrium Fistula: A Case Report
Authors: Muhammad Hasan, Melanie LaVoie
Journal: Circulation (2024)

Introduction: Sinus of Valsalva aneurysm (SVA) accounts for 3.5% of all congenital cardiac anomalies. Rupture occurs in 35% of cases and can lead to life-threatening fistulas, predominantly involving the right ventricle or right atrium. Description of Case: 62-year-old female with hypertension and hypothyroidism presented to the ER with progressively worsening dyspnea over the past week. She also reported worsening lower extremity edema, orthopnea, and paroxysmal nocturnal dyspnea. Chest X-ray showed large pleural effusions. Her ejection fraction was 66% ejection fraction with a fistula between the right sinus of Valsalva and the right atrium on transthoracic echocardiogram (TTE) which was also seen on transesophageal echocardiogram (TEE). Her heart failure was due to the fistula as she had no coronary artery disease on coronary angiogram. She had cardiothoracic surgery for fistula repair. Postoperatively, she developed complete heart block requiring a permanent pacemaker. She had no further complications and was discharged home in good condition. Discussion: SVA affects the right sinus (94%), with the non-coronary (5%) and left sinus (1%) being less commonly involved. Aneurysm rupture typically forms a fistula into the right ventricle (60%), right atrium (29%), left atrium (6%), or left ventricle (4%), and rarely into the pericardial cavity (1%). Symptoms vary by rupture size and location. TTE is the initial diagnostic tool but has limited sensitivity (50%) for detecting fistulas, whereas TEE has a 90% sensitivity. Cardiac MRI and CT can further refine diagnoses, and cardiac catheterization assesses coronary arteries preoperatively. Surgical closure with a patch is the primary treatment for ruptured SVA, significantly improving survival rates compared to non-surgical management.
Abstract 4117646: The Ultimate Test in Hemocompatibility: HeartMate3 Restart After Prolonged Pump Shut Down
Authors: Montana Goral, mary hightower, Michele Edwards, densey varghese, Melanie Thomas, elizabeth hardin, Han Wool Kim, Paris Malensek, Hadi Beaini, Ravi Patel, Patrick O'Hara, Anas Jawaid, Fizza Hussain, Matthias Peltz, Maryjane Farr, Faris Araj
Journal: Circulation (2024)

Introduction: The HeartMate 3 (HM3) LVAD, was shown to have a higher survival free of hemocompatibility related adverse events (HRAE) compared to its predecessors (HM2, HVAD). Superior HM3 outcomes are attributed to wide blood flow pathways coupled with frictionless movement and intrinsic pulsatility, reducing shear stress and blood stasis. It is unknown if improved hemocompatibility can withstand pump restart after prolonged shutdown. We herein report a case of HM3 pump stoppage without subsequent HRAE. Case Presentation: A 41-year-old male underwent HVAD implant in 2019 for advanced non-ischemic cardiomyopathy. This was exchanged to HM3 for recurrent neurological events despite therapeutic anticoagulation. Ten months after exchange, he awakened one morning to find his LVAD had been off for an unknown period but had not heard any device alarms (85dB if on battery power, 165dB if on wall power). Since he felt well he changed to battery power resulting in immediate pump restart. Log file analysis showed pump stoppage 2 am – 10 am, without preceding low flow alarms or power elevations. Management and Outcomes: In the ER INR was 1.5 (2.8 one week prior) and systemic heparin was started. Evaluation included: 1) CT brain without acute infarcts 2) echocardiogram without intracardiac thrombus 3) CT Angiography with patency of the inflow cannula and outflow graft 4) stable serial LDH measurements. The controller was exchanged, and analysis noted normal function. 1-year later the patient is maintained on warfarin and aspirin 325mg without further HRAE. Given the patient’s neurologic history and pump stoppage event, we did not invoke ARIES trial guidance and thus continued aspirin. Conclusion: Pump stoppage occurs when there is complete battery depletion, disconnection of both power leads, or the percutaneous lead from system controller. Our case is unique in that the duration of pump shutdown was 8 hours and INR subtherapeutic, without HRAE in the background of neurologic events on HVAD support. It has been previously reported that complete outflow graft thrombosis can occur shortly after LVAD decommissioning. The HM3 User Manual recommends restarting the pump immediately if off for a few minutes and using clinical judgment for longer durations due to increased risk for thromboembolic events. Our case adds to the paucity of existing data on improved hemocompatibility of the HM3 during rare circumstances of the ultimate test in hemocompatibility: complete pump shut down.
Abstract 4119052: Redefining the phenotypic continuum of cardiovascular disease using machine learning
Authors: Lara Curran, Paolo Inglese, Khaled Rjoob, Kathryn McGurk, Chang Lu, Sean Zheng, Shamin Tahasildar, Soodeh Kalaie, Wenjia Bai, Brian Halliday, Upasana Tayal, Antonio de Marvao, James Ware, Sanjay Prasad, Declan O'Regan
Journal: Circulation (2024)

Background: Current approaches that define cardiovascular disease rely on assignment of traditional diagnostic labels which may not reflect the natural continuum of phenotypic expression, influenced by genetic and environmental modifiers, or adequately identify groups with shared molecular mechanisms. Machine learning can leverage advances in genetic and imaging characterisation to reclassify phenotypic diversity along a continuum, from health to disease. Research Aims: Our study aims to build a tree-like classification of cardiovascular phenotypes in the community where branches represent subjects with shared features, ordered by their severity. Using dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) as exemplar conditions with opposing phenotypes, we aim to demonstrate the interaction between genetic and environmental modifiers of disease expression. Methods: We analysed cardiovascular magnetic resonance (CMR) imaging, electrocardiogram (ECG), biomarkers and clinical data from participants in the UK Biobank. Using unsupervised learning of multiparametric data, we built a tree of phenotypic expression. We projected the risk of DCM and HCM cases, and associated rare and common variant risk, onto the tree structure. Results: Ten main branches were discovered, using data from 41,525 participants (51.7 % female, median age 65 yrs [IQR: 58, 70]). The extremities of branches 1 and 6 were enriched for DCM cases (p &lt;0.05) and participants with reduced ejection fraction and high left ventricular volumes (p &lt;0.05). Compared with subjects at the tree centre, distal participants in branch 1 had increased blood pressure (BP) and body mass index (BMI), whilst those in branch 6 were more likely to have high HbA1c levels and carry a pathogenic DCM variant (p &lt;0.05). The extremity of branch 5 was enriched for HCM cases, rare sarcomeric variants (p = 0.004) and high polygenic risk (p &lt;0.001). Whilst the ends of branches 3 and 9 had high polygenic risk for HCM, they were less likely to have elevated BP and BMI, and had reduced likelihood of HCM expression, compared with branch 5. A phenomapping model was trained to accurately project unseen subjects onto the tree (R 2 0.98). Conclusions: We present a tree-like continuum of cardiovascular phenotypes, providing a novel framework for mechanistic discovery and exploration of genotype-phenotype associations. Phenomapping of unseen subjects enables personalised estimation of genetic and cardiovascular risk.
Abstract 4118410: The Effect of Positive Tilt Table Tests on Long QT Syndrome Diagnosis: A Cross-Sectional Perspective
Authors: Abbas Mohammadi, Mohammad Hossein Nikoo, Hossein Fatemian
Journal: Circulation (2024)

Background: The tilt table test (TTT) serves as a widely adopted diagnostic tool for evaluating syncope of undetermined etiology, with a positive result often indicative of parasympathetic overstimulation. This excessive activation of the parasympathetic system holds the potential to influence QTc measurement not only through rate modulation but also by impacting potassium ionic channels, given that muscarinic activation inwardly rectifies the K+ current. Methods: In this cross-sectional study, 478 patients experiencing syncope of unknown origin underwent evaluation with TTT and 24-hour Holter electrocardiogram monitoring. The Schwartz Score, utilized for diagnosing Long QT syndrome, was computed for all participants. Those with secondary causes of long QT were excluded from the analysis. The association between positive TTT results and Schwartz Score was then examined. Results: A total of 478 patients were enrolled in the study, comprising 208 (43.4%) males and 270 (56.4%) females. The mean age of the patients was 42.43±17.979 years. TTT results were positive in 289 (60.46%) patients and negative in 189 (39.54%) patients. Patients with positive TTT results exhibited a significantly higher mean Schwartz Score compared to those with negative results (2.77±0.08 vs. 1.99±0.12) (P&lt;0.001) (Figure 1). The odds ratio for higher Schwartz scores in the presence of positive TTT results was 4.547. Conclusion: Caution is warranted when diagnosing long QT syndrome as a potential cause of syncope solely based on the Schwartz Score. This study underscores the necessity for potential modifications to the scoring system, acknowledging the impact of tilt table test outcomes on its predictive accuracy. These findings contribute to the ongoing discourse on refining diagnostic approaches for Long QT syndrome in the context of syncope, promoting more accurate and nuanced clinical decision-making.
Abstract 4118183: Anxiety disorder, depression and coronary artery disease: associations and modification by genetic susceptibility
Authors: Shinya Nakada
Journal: Circulation (2024)

Background: Associations of anxiety disorder and depression with coronary artery disease (CAD) are heterogeneous between populations. Research questions: How does genetic susceptibility to CAD alter the associations between anxiety and depression and incident CAD? Aims: To investigate how genetic susceptibility to CAD alters the associations of anxiety and depression with incident CAD, comparing and combining anxiety and depression. Methods: This is a prospective cohort study using UK Biobank. Diagnoses of anxiety disorder and depression before the baseline assessment were ascertained through linked hospital admission data. Incident CAD was ascertained through hospital admission and death certificate data after baseline. CAD polygenic risk score (PRS) was obtained from CARDIoGRAMplus4 and categorised into low, intermediate, and high. Cox proportional hazard models were used to examine associations between anxiety and depression and CAD. The product term of PRS and these mental health conditions, and the relative excess risk due to interaction (RERI), were used to investigate the presence of multiplicative and additive interactions, respectively. Results: Our study included 288,152 participants of whom 54.4% were female, with a mean age of 56.4 years. Both anxiety disorder (HR: 2.24, 95% CI: 1.86–2.70) and depression (HR: 2.04, 95% CI: 1.80–2.32) were associated with CAD after adjusting for sociodemographic confounders. There was an addictive interaction between depression and PRS (RERI: 0.86; 95% CI: 0.06–1.65) such that the association between depression and CAD was strongest among those with a high PRS whilst there was no such evidence for anxiety disorder. Anxiety only (HR 1.69, 95% 1.17–2.45), depression only (HR 2.01, 95% CI 1.62–2.49) and concomitant anxiety and depression (HR 3.51, 95% CI 2.26–5.45) were associated with CAD even among people with a low PRS. Lifestyle mediators attenuated all these associations across PRS categories. Conclusions: CAD genetic susceptibility might partly contribute to the clustering of depression and CAD but does not provide a full explanation, nor does it explain the association between anxiety disorder and CAD. Therefore, other mechanisms should be explored.
Abstract 4123872: Unsupervised clustering analysis of large-scale proteomics data identifies molecular phenogroups of heart failure in a population-based cohort
Authors: Carolina Downie, Joe Shearer, Kayode Kuku, Maryam Hashemian, Suzette Bielinski, Jungnam Joo, Veronique Roger
Journal: Circulation (2024)

Background: Heart failure (HF) is a heterogeneous syndrome with high mortality. Previous work characterizing HF subgroups primarily relied on clinical data to cluster patients, an approach constrained by the boundaries of documented clinical features. Clustering based on biomarker data, such as proteomics, may provide insights into underlying molecular processes. However, few studies have used this approach, and all used targeted cardiovascular proteomics panels and a restricted HF ejection fraction group. Hypothesis: We used unsupervised clustering analysis to characterize molecular phenogroups in a population-based HF cohort using a large-scale array of circulating plasma proteins. We hypothesized that distinct proteomic-defined phenogroups would exhibit differences in clinical characteristics, mortality, and protein expression. Methods: We measured 7151 SOMAmers (Slow off-rate modified aptamers) targeting human proteins via the SomaLogic 7K SomaScan assay in 1351 HF patients. After feature selection, 831 SOMAmers were used in k-means clustering of patients via R package “ConsensusClusterPlus.” Phenogroups were compared for clinical characteristics, all-cause mortality, and protein expression. Results: Three phenogroups were identified, exhibiting different clinical characteristics ( Table 1 ) and survival probabilities (5-year survival probability in phenogroup 1: 65% [61%, 68%], phenogroup 2: 45% [40%, 51%], and phenogroup 3: 26% [22%, 30%]). In covariate-adjusted Cox models, membership in phenogroups 2 and 3 was significantly associated with increased rate of mortality compared to phenogroup 1. Phenogroups did not differ by ejection fraction or New York Heart Association class. Pathway overrepresentation analysis of differentially expressed SOMAmers identified pathways associated with inflammatory response and immune cell trafficking. Conclusions: Unsupervised clustering analysis using large-scale proteomics data identified three HF phenogroups with different proteomic signatures, clinical characteristics, and outcomes. Future work is necessary to elucidate how molecular differences contribute to heterogeneity in HF to improve risk stratification beyond current recommended clinical guidelines.
Abstract 4119213: A Novel Animal Model for Pulmonary Hypertension: Lung Endothelial Specific Deletion of Egln1 in Mice
Authors: Bin Liu, Dan Yi, Karina Ramirez, Michael Fallon, Zhiyu Dai
Journal: Circulation (2024)

Background: Pulmonary arterial hypertension (PAH) is a disastrous disease that is characterized by high blood pressure in the pulmonary arteries which has the potential to lead to heart failure over time. Previously, our lab found that endothelial-specific knockout of Egln1 , encoding prolyl 4-hydroxylase-2 (PHD2), induced spontaneous pulmonary hypertension (PH). Recently, we elucidated that Tmem100 is a lung-specific endothelial gene using Tmem100 CreERT2 mice. We reason that lung endothelial-specific deletion of Egln1 could lead to the development of PH without affecting other organs’ Egln1 gene expression and defect. Methods: Tm em100-CreERT2 mice were crossed with Egln1 flox/flox mice to generate Egln1 f/f ; Tmem100 CreERT2 (LiCKO) mice. Western blot and immunofluorescent staining were performed to verify the knockout efficacy of Egln1 in multiple organs of LiCKO mice. PH phenotypes including hemodynamics, right heart size and function, and pulmonary vascular remodeling were evaluated by right heart catheterization and echocardiography measurement. Results: Tamoxifen treatment induced Egln1 deletion in the lung ECs but no other organs in adult LiCKO mice. LiCKO mice exhibited an increase in right ventricular systolic pressure (RVSP, ~35 mmHg) and right heart hypertrophy. Echocardiography measurement showed right heart hypertrophy and cardiac and pulmonary arterial dysfunction. Pulmonary vascular remodeling including pulmonary wall thickness and muscularization of distal pulmonary arterials was enhanced in LiCKO mice compared to wild-type mice. Conclusions: Tmem100 promoter-mediated lung endothelial knockout of Egln1 in mice develops spontaneous PH. LiCKO mice could be a novel mouse model for PH to study lung and other organ crosstalk.
Abstract 4115669: Single-cell and Spatial Transcriptomics Identified Fatty Acid-binding Proteins Controlling Endothelial Glycolytic and Arterial Programming in Pulmonary Hypertension
Authors: Bin Liu, Dan Yi, Shuai Li, Karina Ramirez, Xiaomei Xia, yanhong cao, Vinicio Dejesus, Christopher Glembotski, Zhiyu Dai
Journal: Circulation (2024)

We are seeking to elucidate the endothelial fatty acid metabolism role for obstructive vascular remodeling in the pathogenesis of PAH. In this study, we bred a severe mouse model of PH Egln1 Tie2Cre mice with Fabp45 -/- mice to generate Egln1 Tie2Cre / Fabp45 -/- mice. We applied single-cell RNA sequencing (scRNA-seq) to profile the pulmonary cells in Egln1 Tie2Cre mice and Egln1 Tie2Cre / Fabp45 -/- mice. Human hPAEC from idiopathic PAH patients and healthy donors were used to measure fatty acid-binding protein 4 and 5 (FABP4 and FABP5) expression via sc-RNA seq and spatial transcriptomics. siRNA-mediated knockdown of FABP4 and FABP5 and lentivirus-mediated FABP4 and 5 overexpression were performed to study cell proliferation, apoptosis, and glycolysis. Our scRNA-seq analysis demonstrated that both FABP4 and 5 were highly induced in the ECs of Egln1 Tie2Cre mice. PAECs from IPAH patients also showed higher expression of FABP4 and 5. Knockdown of FABP4-5 reduced EC proliferation, starvation-induced Caspase 3/7 activity, and glycolysis. Overexpression of FABP4-5 promoted EC glycolysis and proliferation. Genetic deletion of Fabp4 and 5 in Egln1 Tie2Cre mice exhibited a reduction of RVSP, RV hypertrophy, and reduction of EC glycolysis gene programming compared to Egln1 Tie2Cre mice. In conclusion, we found that FABP4 and 5 control EC glycolysis and contribute to the development of PAH.
Abstract 4116558: Navigator-driven Recommendations for Palliative Care Consults for Patients with Heart Failure and High Predicted Mortality
Authors: Matthew Anderson, Austin Seals, Amy Taylor, Taylor Simmons, Olivia Gilbert
Journal: Circulation (2024)

Background: Palliative care (PC) engagement can improve quality of life, reduce hospital costs, and enhance symptom control for individuals with heart failure (HF). For certain HF patients, PC can address symptoms and improve quality of life. However, referrals to PC often occur late, delaying benefits. Hypothesis: We hypothesize that a standardized recommendation for inpatient PC consultation will increase PC consultation rates and improve 30-day readmission without an impact on 30-day mortality rates. Methods: This interrupted time series study focused on high-risk HF patients at Atrium Health Wake Forest Baptist. The cohort included patients in the Golden Hearts Program, which is a local program to identify HF patients at elevated risk for 30-day readmissions and to accelerate resources to support their transitions. Baseline data were from patients 5 months before September 1, 2023, and the intervention group were from patients 5 months afterward. A standardized message recommending inpatient PC consultation was sent to attending physicians for patients with ESCAPE scores ≥4. Recommendations were also discussed at multidisciplinary rounds with senior residents. The primary outcomes were inpatient palliative care consultation and discharge to Hospice. Secondary outcomes were 30-day readmissions and 30-day mortality. Outcome measures were assessed post-discharge using Chi-square and T-test analyses. Results: The baseline group had 203 patients; the intervention group had 213. Post-intervention, PC consultation rates decreased from 12.3% to 8% (p=0.19), Discharge to hospice decreased from 2% to 0.9% (p=0.05), 30-day mortality decreased (8.4% vs 7%, p=0.74), and 30-day readmission dropped from 23.6% to 15% (p=0.04). The average length of stay remained 5.7 days in both groups. Limitations included provider buy-in and a limited time period. Conclusion: Though the intervention aimed at targeted PC consult recommendations for advanced HF patients led to reduced 30-day readmissions, there was a not a statistically significant impact on palliative care consultation or mortality.
Abstract 4115139: The Clinic Ottakring – Lipid Registry: a Contemporary Single-Center Real-World Analysis from a Tertiary Hospital
Authors: Patrick Weltler, Edita Pogran, Paul Felix Harbich, Achim Burger, Georg Neubauer, Kurt Huber
Journal: Circulation (2024)

In the real world only about 20 % of patients with ASCVD are at the target range, as shown by the SANTORINI trial (1). Therefore, there is still a great need for the improvement of lipid-lowering therapy (LLT). Our Lipid Registry was set up as a retrospective study including patients who visited our outpatients ward focusing on lipid-lowering therapy (LLT). The indications were: low-density lipoprotein cholesterol (LDL-c) &gt; 130 mg/dL in LLT- naive patients with acute coronary syndrome (ACS), coronary artery disease (CAD) not on optimal LLT, familial hypercholesterolemia and LLT intolerance. We collected baseline characteristics as well as laboratory parameters of these patients during their visits. The dual LLT (high-potency statin and ezetimibe) was initiated in every patient during the hospitalization, if not contraindicated, as target variable we used non-HDL-C. In total 181 patients were included, of which 136 (75.1%) patients visited our clinic for control purposes. Patients who didn’t visit the clinic were predominantly men and had no or few pre-experiences with LLT. Fourty-one (36.9%) patients had a BMI&gt;30, 126 (92.6%) of patients had CAD of which 85 (63%) had the diagnosis of a recent ACS. Arterial hypertension was present in 78.7% and diabetes mellitus type 2 in 23.5% of cases. At the 1 st visit to our LLT department 4-6 weeks after dismission from the hospital, 86 patients (61.9%) reached the recommended (ESC/EAS 2019) non-HDL-C goal. At the 2 nd visit (8-12 weeks after index hospitalization), 117 patients (86.2%) and at the 3 rd visit 120 patients (88.2%) reached their target. The analysis of patients initially presenting with ACS showed that 60 (69.8%) of them after 4-6 weeks and 77 (90.6%) patients after 8-12 weeks reached the recommended non-HDL-c goal. Among the study population 108 (79.4%) of patients, and 81 (95.3%) of ACS patients received dual LLT immediately during the index event. After the first visit, 31 (36.5%) of ACS patients needed the addition of the third lipid-lowering drug to achieve the recommended goal (see attached tables). Our strategy for managing hyperlipidemia in patients with a very-high cardiovascular risk showed high achievement of the non-HDL-C goal as recommended by the recent ESC guidelines in contrast to real-world data. We were able to demonstrate, that the strategy based on the idea to treat high-CV risk patients early and strong is the way to reach the treatment goal in a high percentage of patients (2).