tbuckley/cabot-search huggingface dataset:
Abstract 4147467: Combined Heart and Liver Transplantation in the Failing Fontan: Systematic Review and Single-arm Meta-analysis
Authors: Vanessa Karlinski Vizentin, Cynthia Mesquita, Iuri Ferreira Felix, Elisio Bulhoes, Vanio do Livramento Junior Antunes, Rebecca Ameduri, Jonathan Johnson
Journal: Circulation (2024)

Background: The Fontan procedure has transformed the management of congenital heart defects (CHD) characterized by single ventricle physiology, yet it predisposes individuals to Fontan-associated liver disease (FALD), potentially leading to end-stage liver disease (ESLD). Combined heart and liver transplantation (CHLT) emerges as a therapeutic option, but evidence on its efficacy, safety, and outcomes remains limited. Objectives: This systematic review and single-arm meta-analysis aims to comprehensively evaluate the literature on CHLT in Fontan patients, focusing on patient characteristics, perioperative outcomes, and post-transplant morbidity and mortality. Methods: A systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials was conducted following PRISMA guidelines. Studies meeting the intervention of CHLT in Fontan patients were included and data were collected and synthesized using proportion meta-analysis techniques. Statistical analysis was carried out using R software. Results: Four studies met inclusion criteria, comprising 67 Fontan patients undergoing CHLT. All included studies were observational retrospective cohorts performed in the United States. One-year survival rate post-CHLT was 84% (95% CI 66%-94%), Figure 1A. Rates of liver and heart graft rejection were low 10% (95% CI 3%-33%) and 8% (95% CI 2%-31%), respectively, Figure 1B. Postoperative complications included acute kidney injury 72% (95% CI 46%-88%), temporary dialysis 31% (95% CI 14%-55%), neurologic events 14% (95% CI 5%-34%), infection 24% (95% CI 6%-63%), and unplanned medical procedures 41% (95% CI 24%-60%), Figure 1C. Conclusion: CHLT in Fontan patients demonstrates promising survival rates, but graft rejection and postoperative complications pose challenges. The rate of renal complications is particularly notable and requires further evaluation. Future research should prioritize comparative different management strategies and long-term follow-up to refine protocols and optimize outcomes.
Abstract Or111: Association of hypertonic saline treatment with change in cerebral oxygen extraction after cardiac arrest
Authors: Laura Faiver, Patrick Coppler, Cecelia Ratay, minjung chae, Kate Flickinger, Lee Eun, Changshin Kang, Jonathan Tam, Jonathan Elmer
Journal: Circulation (2024)

Introduction: Elevated jugular bulb venous oxygen saturation (SjvO2) after cardiac arrest may occur because of diffusion-limited oxygen extraction secondary to perivascular edema. This edema may respond to treatment with hypertonic saline (HTS), thereby decreasing the barrier to oxygen diffusion. Alternatively, SjvO2 can rise when cerebral metabolic rate decreases, which is not affected by HTS. Electroencephalography (EEG) may differentiate between these etiologies and thus identify patients for whom treatment with HTS will improve oxygen extraction. Hypothesis: Post-arrest patients with elevated SjvO2 would have improved oxygen extraction after treatment with HTS and qualitative EEG could be used to predict treatment responsiveness. Methods: We conducted a retrospective multicenter cohort study including comatose survivors of cardiac arrest who had intermittent SjvO2 monitoring. We performed a Kruskal Wallis test comparing mean SjvO2 values within the first 24 hours after arrest between survivors and non-survivors. In the subgroup of patients who were treated with HTS for SjvO2 &gt;75% and were EEG monitored, we quantified compared SjvO2 before and after HTS using a multivariable mixed-effects regression treating HTS as a fixed effect, adjusting for mean arterial pressure, partial pressure of arterial oxygen and partial pressure of carbon dioxide. We classified pre-treatment EEG patterns as benign or indicative of potential metabolic failure (generalized suppression, burst suppression, or discontinuous with superimposed rhythmic or periodic patterns) and tested for an interaction of EEG with HTS. Results: We included 131 patients of whom 115 had SjvO2 data within 24 hours. Mean SjvO2 was higher (p = 0.0002) in non-survivors (77% [SD ±11]) than survivors (71% [SD ±11]). Twenty-one subjects received 28 HTS treatments. We found an independent association of HTS with decreased SjvO2 (ß = -3.8%; 95% CI, -6.4 to -1.2; p = 0.004). There was no interaction between pre-treatment EEG and HTS predicting SjvO2. Conclusions: Early elevated SjvO2 is associated with mortality at hospital discharge. SjvO2 decreased following treatment with HTS, suggesting diffusion limited oxygen extraction secondary to modifiable perivascular edema. As mechanisms of secondary brain injury after cardiac arrest vary among patients, a precision approach to treatment is essential; however, we did not identify evidence to support the use of qualitative EEG to guide patient selection for treatment.
Abstract 4146716: Radial Versus Femoral Access for Mechanical Thrombectomy in Patients with Stroke: A Systematic Review, Meta-Analysis and Meta-Regression
Authors: Ramez Odat, Ayham Hussein, Muhammad Idrees, Abdullah Aldalati, Bashar M. Al Zoubi, Dania Haneyah, Rubab Zahra, Sakhr Alshwayyat, Jehad Yasin, Cameron Sabet, Dang Nguyen
Journal: Circulation (2024)

Background: Femoral access is predominantly used for mechanical thrombectomy in stroke patients with large vessel occlusions. Following interventional cardiology guidelines, routine radial access has been proposed as an alternative, though its safety and efficacy remain controversial. We aimed to evaluate the efficacy and safety of radial versus femoral access for mechanical thrombectomy in patients with stroke. Hypothesis: In mechanical thrombectomy for stroke patients with large vessel occlusions, could the transradial access (TRA) result in comparable efficacy but fewer access site complications compared to transfemoral access (TFA)? Methods: A systematic search was performed in PubMed, Scopus, Cochrane, Embase, and Web of Science databases from inception to May 2024, to identify studies measuring the efficacy and safety of radial versus femoral access for mechanical thrombectomy in patients with stroke. The meta-analysis was performed using the Review Manager and Open Meta Analyst. Results: Ten studies (2,277 participants) were included in the review. There were no significant differences between radial and femoral access in terms of successful recanalization (0R: 1.01; 95% CI, 0.59,1.73; p=0.98), complete recanalization (OR: 1.08; 95% CI, 0.60,1.94; p=0.81), favorable functional outcomes (0R: 0.86; 95% CI, 0.53,1.41; p=0.56), first-pass reperfusion (OR: 0.89; 95% CI, 0.67,1.19; p=0.44), number of passes (MD: 0.10; 95% CI, -0.13,0.33; p=0.4), access-to-reperfusion time (MD: -3.92; 95% CI, -9.49,1.65; p=0.17), or symptomatic intracranial hemorrhage (OR: 0.95; 95% CI, 0.55,1.65; p=0.86). However, access site complications were significantly less frequent in the TRA group as compared with the TFA group (OR: 0.21; 95% CI, 0.08,0.60; p=0.004). Meta-regression showed no significant associations for publication year, mean age, gender, or baseline NIHSS scores with clinical outcomes. Conclusion: This meta-analysis indicates that TRA and TFA provide comparable outcomes in mechanical thrombectomy for acute ischemic stroke, with TRA resulting in fewer access site complications. Further large-scale randomized trials are recommended to confirm these findings and potentially support a shift towards TRA in neurovascular procedures.
Abstract 4146877: Percutaneous coronary intervention in cancer patients with chronic coronary artery disease is associated with lower major cardiovascular events
Authors: Brunna Pileggi, Andre Franci, Roberta Saretta, Luciano Baracioli, Luciano Drager, Roberto Kalil Filho
Journal: Circulation (2024)

Background: The interaction between cancer and coronary artery disease (CAD) is well established, primarily due to shared risk factors, chronic inflammation, and complications related to cancer therapies. Prior studies regarding percutaneous coronary intervention (PCI) in patients with chronic CAD have never demonstrated consistent reduction in hard endpoints. Nevertheless, cancer patients are frequently excluded or underrepresented in major clinical trials that address this matter. Objectives: To evaluate whether PCI in patients with chronic CAD and cancer could impact outcomes. Methods: Observational, retrospective cohort study with data from the TriNetX platform, an international research network database, which provides access to electronic medical records across large health care organizations. Inclusion criteria were age ≥18 years, diagnosis of chronic CAD and a concurrent cancer diagnosis within one year. Patients with acute coronary syndrome (ACS) and hematologic cancers were excluded. Participants were divided into two groups: 1) those who underwent PCI within this first year after the diagnosis of cancer and 2) those who did not receive intervention. The primary outcome was major adverse cardiovascular events (MACE), defined by all-cause mortality, non-fatal myocardial infarction, and non-fatal ischemic stroke over a five-year period. Propensity score matching was conducted using variables such as age, gender, types of cancer, hypertension, previous cerebrovascular disease, diabetes, dyslipidemia, tobacco use, left ventricular ejection fraction, and peripheral artery disease. Results: A total of 741,184 patients were included, 12,189 in group 1 and 728,995 in group 2. The mean age was 72±9 and 73±10 years, respectively. Most patients were men, and most common cancer sites were prostate, digestive system, urinary tract and lungs. The primary analysis showed a five-year incidence of MACE of 27.6% in group 1 vs 31.1% in group 2 [OR 0.86 (95% CI 0.81-0.88), p&lt;0.0001]. After propensity score matching, the incidence of MACE was 27.6% vs 29.2% [OR 0.92 (95% CI 0.87-0.98), p=0.006]. Kaplan-Meier event-free survival curves before and after propensity matching are shown in the figure. Conclusion: PCI in patients with chronic CAD and cancer was associated with a lower incidence of MACE in 5 years in a large real-world international database. Randomized controlled trials including patients with cancer are urgently needed to further investigate these outcomes.
Abstract 4147177: Unveiling the Novel Therapeutic Role of PDE10A-Mediated Functional Protein Complex in Cardiac Hypertrophy
Authors: Si Chen, Xinyue Fan, Sumin Xu, Nichen Zhu, Hangchuan Shi, Chen Yan
Journal: Circulation (2024)

Heart failure is a leading cause of death in the United States, and is associated with significant myocardial deterioration. cAMP and cGMP play critical roles in cardiovascular biology and disease. cAMP and cGMP form multiple spatially discrete and functionally distinct cyclic nucleotide 'pools,' each associated with unique multi-protein complexes comprising cyclases, PDEs, and other signaling molecules, contributing to distinct biological functions. Phosphodiesterase 10A (PDE10A) is able to hydrolyze both cAMP and cGMP. Our previous published study provides strong evidence supporting a critical role of PDE10A induction in pathological cardiac remodeling and suggest the therapeutic potential of PDE10A inhibition. However, the cellular and molecular mechanisms and the sources of cyclic nucleotides that are regulated by PDE10A remain unknown. Our encouraging results revealed that the anti-hypertrophic effect of PDE10A inhibition/deficiency is dependent on cAMP/PKA signaling in cultured adult mouse cardiomyocytes (CM). We identified the existence of adenosine-dopamine receptor (A 2A R-D 2 R) heterodimer and the connection of PDE10A with A 2A R-D 2 R signaling, by which PDE10A inhibition uniquely promotes heterodimerization of A 2A R-D 2 R, and biased activation of D 2 R/β-arrestin2 (βarr2) through A 2A R/cAMP/PKA-mediated phosphorylation of D 2 R in CMs. Consistent with what we found in CM, disruption of A 2A R-D 2 R heterodimer or D 2 R/ βarr2-biased activation significantly abolish the protective effects of PDE10A inhibition on cardiomyopathy and dysfunction in vivo . Additionally, we found that activation of D 2 R/βarr2 signaling attenuates stress-induced cardiac remodeling and dysfunction in vivo . Together, these results strongly suggest that PDE10A plays a critical role in pathological cardiac remodeling by promoting CM hypertrophy through regulation of A 2A R-D 2 R/βarr2 biased signaling. Targeting PDE10A and GPCR heterodimerization in CMs may represent a novel therapeutic strategy for treating cardiac diseases.
Abstract 4146737: AmyNet: a Novel Deep Learning Imaging Approach to Identify Incidental Myocardial Uptake Indicative of Cardiac Amyloidosis on Whole Body 99Tc-Bone Scintigraphy Imaging
Authors: Abhijit Bhattaru, Chaitanya Rojulpote, Mahesh Vidula, Jeffrey Duda, Elizabeth Thompson, Sophia Swago, James Gee, Janice Pieretti, Brian Drachman, Sharmila Dorbala, Walter Witschey, Paco Bravo
Journal: Circulation (2024)

Introduction: Whole-body scintigraphy (WBS) is frequently performed for oncological indications but also has high sensitivity for incidental detection of transthyretin amyloid cardiomyopathy (ATTR-CM), which may be overlooked. Goal: Develop an algorithm that combines chest computed tomography (cCT) and WBS to identify incidental ATTR-CM in a large healthcare system. Methods: We included 3 cohorts: 1) 77 patients from Brigham and Women’s Hospital with high prevalence of patients positive for ATTR-CM (BWHC), 2) 982 continuous cohort of patients imaged with WBS at PennMedicine for oncological indications from 2010-2020 (PennC), and 3) 5 patients with proven ATTR-CM uptake on WBS when imaged for oncologic indications from 2021-2024 (PennC+). Using a U-Net model trained with Dice score, the AmyNet algorithm automatically segmented cCTs with regions of interest (ROIs) around the entire heart (ventricles, atria, blood pool). Maximal intensity projections of cCTs in the coronal plane were registered to WBS using rigid transformations from the ANTs library. Multiple template reconstructions of only BWHC projections augmented registration due to limited field of view of cCT by providing an initial alignment to the thorax. Transformations were applied to heart ROIs to identify the location on WBS. A modified contralateral ratio was calculated by taking the lateral 1/3 and inferior 2/3 region to avoid sternum and atria and reflecting it across the vertical axis. A cutoff ratio of 1.15 was established as positive for ATTR-CM. Results: Machine-generated and expert volumes were comparable (1071vs1087mL; p=0.74) with a Dice similarity index of 0.92±0.07. AmyNet had a 94% accuracy with 100% sensitivity and 90% specificity in detecting ATTR-CM in BWHC with positive patients having higher contralateral ratios (1.57±0.49 vs 1.01±0.18, p&lt;0.0001). Screening of PennC identified one patient (0.1%) with myocardial uptake, which was confirmed ATTR-CM upon evaluation for HFpEF. All 5 PennC+ patients were detected positive for uptake by AmyNet. Conclusion: We created the first algorithm that leverages cCT data and WBS to detect incidental cardiac uptake suggestive of ATTR-CM in patients underdoing scans for other non-cardiac indications.
Abstract 4147136: Functional Consequences and Phenotypic Manifestations of <i>KCNJ2</i> Variants in Andersen-Tawil Syndrome
Authors: Cassandra Hartle, Ian Dinsmore, Tooraj Mirshahi, Jonathan Luo, Robert Mangano, Bryn Moore
Journal: Circulation (2024)

Introduction: Andersen-Tawil Syndrome (ATS) is a rare genetic disorder characterized by periodic paralysis, skeletal abnormalities, and elongated QTc. ATS is caused by mutations in KCNJ2 , which encodes the inwardly rectifying Kir2.1 channel that constitutes IK 1 in the heart. Out of 2.3 million subjects in our EHR, only 3 had an ATS diagnosis, confirmed by clinical genetic testing. Due to the low prevalence and variable expressivity, diagnosing ATS is challenging. Hypothesis: ATS is often misdiagnosed and protein truncating variants (PTV) in KCNJ2 are not sufficient to cause disease. Methods: For 173,589 patients with exome sequencing in the EHR we identified all KCNJ2 variants with allele frequency &lt;0.01 and performed gene burden testing using REGENIE. We performed chart reviews and functional testing on all subjects with PTVs and any missense variant with at least one carrier with LQTS or ATS. Variants were tested by whole cell patch clamp, western blot, and immunofluorescence for function, expression and localization, respectively. Dominant negative effect was assessed by co-expressing the wild-type channels. Results: Gene burden analysis revealed cardiac arrhythmias as the only phenotype significantly associated with alpha-missense predicted pathogenic KCNJ2 variants. We found 11 carriers of 4 PTVs (R40Ter, E118Ter, E241fs, L368fs). We also found 5 carriers of 4 missense variants V4E, T75M, R218W, and R312H, which had at least one diagnosis of LQTS or ATS. In whole-cell patch clamp, PTVs did not produce functional channels or affect the function of co-expressed wild-type channels. None of the PTV carriers had ATS. Patients with LQTS diagnoses and PTV variants often had secondary underrated conditions, which can result in elongated QT intervals. V4E showed no functional deficits or dominant effects, and the carrier lacked ATS phenotype with a LQTS diagnosis due to an acute electrolyte imbalance. Variants T75M, R218W, and R312H produced small currents and exhibited dominant negative effects when co-expressed with WT channels. T75M reduced current size and altered channel rectification, and R218W and R312H reduced PIP 2 interactions. Four carriers of these missense variants, including a mother-son pair with the T75M variant, manifested various ATS-related phenotypes. Conclusions: Kir2.1 protein truncation alone does not result in pathogenicity. We propose missense variants in KCNJ2 exerting a dominant-negative effect could result in an ATS phenotype.
Abstract 4147211: Machine Learning Models for Predicting In-Hospital Mortality in Acute Aortic Dissection Patients with Malperfusion
Authors: Yanda Zhang, Hang Xing, Ting Wang, Bo Zhang, Jing Yuan, Long Wang
Journal: Circulation (2024)

Introduction: Acute aortic dissection (AAD) remains a critical cardiovascular emergency with high in-hospital mortality, especially in patients with malperfusion syndromes. Accurate prediction of in-hospital mortality in these patients is crucial for improving clinical decision-making and patient outcomes. This study evaluates the performance of various machine learning (ML) models in predicting in-hospital mortality among AAD patients with malperfusion. Methods: The study included 451 acute aortic dissection with malperfusion from Henan Provincial Chest Hospital from August 2020 to September 2023. The dataset included demographic, clinical, laboratory results, and treatment strategies. Multiple ML models were developed and validated, including k-Nearest Neighbor (KNN) and Extreme Gradient Boosting Machine (XGB). Model performance was assessed using sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC-ROC). Results: Our results demonstrated that the XGB model achieved the higher AUC-ROC (0.75, 95% CI: 0.73, 0.78), indicating excellent discriminative ability. KNN model showed lower AUC-ROC (0.66, 95% CI: 0.63, 0.68) but robust performance. Conclusions: XGB models offered promising tools for predicting in-hospital mortality in AAD patients with malperfusion. These models can assist clinicians in identifying high-risk patients and tailoring treatment strategies to improve survival outcomes.
Abstract Or105: Preparing paramedics for patient- and family-centered resuscitation using an ABCD framework
Authors: Carolina Tennyson, John Oliver, Karen Jooste, Jeff Maxin
Journal: Circulation (2024)

Introduction: Data around Family Presence During Resuscitation (FPDR) and the Family Facilitator role are rapidly evolving in inpatient care settings. Yet, there is little formal preparation available for pre-hospital clinicians. A large Canadian paramedic group identified this gap in preparation for FPDR and requested practical, practice-changing education for their clinicians. This project aimed to develop and deliver virtual education regarding patient- and family-centered care using current FPDR evidence and foundational care theories. Additionally, we aimed to evaluate the learner's baseline knowledge, comprehension of the content, and perspective of the framework’s application to practice. Methods: Three interprofessional resuscitation experts used current FPDR evidence and theories to develop the ABCD framework. The purpose of this simple schema is to provide memorable mental cues to prepare resuscitation team members for patient- and family-centered care during cardiac arrest. The ABCD tool emphasizes (A) Awareness of the family facilitator role and needs of the family, (B) Being Present emotionally and physically, (C) Connecting patients and family to the team and other resources, and (D) Debriefing and, in the case that ROSC is not achieved, leading a Pause to recognize the life lost. This framework was introduced during an hour-long pilot session for 75 Paramedics in a large Canadian province. The learning objectives included (1) identifying ways to be emotionally present, (2) communicating effectively with families during and after cardiac arrest care, and (3) recognizing the benefits of real-time reflection and team debriefing. An online survey was used to evaluate the impact of this virtual education on the participants' confidence in their communication skills and caring for family members during resuscitation. Results: Exposure to the ABCD framework positively influenced the confidence with which paramedics responded to families during resuscitation. Attendees responded positively to case studies; many said they felt strongly that they could lead a Pause in the case of patient death and planned to do so. At 3 months post-education, most respondents had already applied the content to their clinical practice. Conclusion: The ABCD framework demonstrates potential to prepare interprofessional learners to provide patient- and family-centered care during resuscitation, and this work represents a first step to validating the framework’s content.