tbuckley/cabot-search huggingface dataset:
Abstract 17643: Pharmacist-Driven Inpatient to Tele-Clinic Transitions of Care: The PICTOC Quasi-Experiment to Reduce 30-day Readmissions in Patients With Heart Failure
Authors: Katherine E Di Palo, Joseph Manganelli, Abhishek Shah, Allison Stark, Jeffrey M Weiss
Journal: Circulation (2023)

Introduction: Successful transitional care models leverage the same clinician, typically nurses, to deliver and coordinate interventions across settings for patients with heart failure. However, pharmacists may be well-suited to lead these efforts given that medication-related issues are often drivers for 30-day readmission. We implemented a pharmacist-driven inpatient to tele-clinic transitions of care (PICTOC) program and evaluated its impact on readmissions at an academic medical center. Methods: Pharmacists provided hospital-based transitional care services two half-days per week between June 2020 and September 2022. They identified patients admitted for heart failure who were established at or referred to specific primary care practices. Patients were prioritized by discharge date and interventions included medication optimization, education, appointment scheduling within 14 days, and a post-discharge telemedicine visit with the pharmacist. A quasi-experimental design was used to compare the 30-day readmission rate in PICTOC group to a control group of patients who met eligibility criteria but were discharged prior to receiving the intervention. Intention-to-treat and per-protocol analyses were performed using Chi-square test. Results: There were 1346 patients included. The mean (SD) age was 67.0 (13.8) years, 51.3% were male and 503 patients received the PICTOC intervention. The 30-day readmission rate in the intention-to-treat group was 15.5% compared to 17.9% in the control group (p=0.25). Among the 75% of patients who attended the pharmacist telemedicine visit per protocol, the readmission rate was 13.5% (p=0.059). Patients in PICTOC group had higher rates of scheduled follow-up with primary care (59.2% vs. 53.7%, p=0.048) and cardiology (48.7% vs. 37.6%, p=0.0001). Appointment attendance with primary care was significantly higher in the PICTOC group (72.5% vs. 61.8%, p=0.0023) and trended higher with cardiology (69.4% vs. 65.9%, p=0.39). Conclusion: The PICTOC program improved transitional care quality and outcomes among patients with heart failure. Additional analyses of this novel care delivery model are warranted.
Abstract 327: Implementation of Bronchoalveolar Lavages as a Quality Improvement Initiative in Out-of-Hospital Cardiac Arrest Patients
Authors: Andrea Jonsson, David Roach, Thomas Rohan, Alexandra Weissman
Journal: Circulation (2023)

Patients who suffer OHCA are at risk for early onset pneumonia due to loss of airway protection, emergency airway access and intubation, CPR, mechanical ventilation, among other complications. It is difficult to accurately diagnose early onset pneumonia post OHCA due to multi-organ dysfunction post arrest and radiography findings confounded by non-infectious inflammation from CPR and aspiration. As a result, a substantial number of patients receive empiric antibiotics. A bronchoalveolar lavage (BAL) can screen for the presence of bacteria in the lungs and aid in identifying the incidence of early onset pneumonia after OHCA. We implemented a quality improvement (QI) initiative to collect a BAL on initial patient presentation to our hospital in May 2018. We conducted an observational, retrospective study to assess the impact of BAL implementation on empiric antibiotic prescribing. We used a rigorous study definition of pneumonia requiring at least two of the following positive within the same 24-hour period: BAL, chest radiography, and/or a fever &gt;38°C. We compared rates of antibiotic prescription in the first 7 days of hospitalization for patients receiving a BAL to those without, as well as rates of antibiotic prescriptions before and after implementation of the BAL QI initiative. Implementation of initial BAL collection was successful and resulted in a 66% increase of BALs (from 44 to 73 BALs) collected compared to an average from the prior 2 years. We hypothesized rates of antibiotic prescription would decrease post-implementation of BAL collection; however, there was no statistically significant change in rate of antibiotic prescription (Figure 1) over the initial 7-day hospitalization period X 2 ( Df = 1, N = 3247) = 0.68, p = 0.54. Over 80% of patients with pneumonia received antibiotics, roughly 60% of OHCA patients received antibiotics despite no pneumonia diagnosis by any definition. Further study is needed to alter these practices and reduce antibiotic overuse.
Abstract 15747: AMPK Cysteine Oxidation by SOD3-Derived H <sub>2</sub> O <sub>2</sub> Mediates Exercise-Induced Restoration of Skeletal Muscle Angiogenesis in Type2 Diabetes
Authors: Sudhahar Varadarajan, Kareem Abdelsaid, Malgorzata McMenamin, Tohru Fukai, Masuko Ushio-Fukai
Journal: Circulation (2023)

Background: Exercise restores decreased capillary density in skeletal muscle (SKM) (capillary rarefaction) in type2 diabetes (T2D) that has eNOS uncoupling/excess O 2 - , which is required for treatment of diabetic peripheral vascular disease (PAD) via unknown mechanisms. AMP-activated protein kinase (AMPK) is a key angiogenic/metabolic kinase mainly regulated by phosphorylation and is required for baseline, but not exercise-induced capillary density in SKM under healthy conditions. AMPK senses H 2 O 2 signal to increase its activity via oxidative modification of Cys299/304 in vitro. In addition, extracellular SOD (SOD3) that catalyzes the dismutation of O 2 - to H 2 O 2 is increased in response to exercise. However, the role of AMPK and SOD3 in exercise-induced SKM angiogenesis in T2D has not been reported. Oxidation of Cysteine residues to generate cysteine sulfenic acid (Cys-OH) is a key event in H 2 O 2 -mediated signaling. Results: Here we show that reduced CD31+ capillary density in SKM of high fat diet-induced T2D mice was restored (2.4-fold) by voluntary wheel exercise training (2 weeks) with enhanced SOD3 activity (224%) and extracellular H 2 O 2 levels (3.2-fold). Of note, exercise in T2D mice increased AMPK activity (by p-ACC) via inducing CysOH formation of AMPK (3.6-fold), but not p-AMPK induction, which was inhibited by SOD3 -/- /T2D mice that reduced exercise-induced H 2 O 2 . To demonstrate functional significance of AMPK Cys oxidation, we generated CRISPR/Cas9-genome editing “redox-dead” AMPK-Cys299/304Ala (AMPK-C/A) knock-in (KI) mutant mice and found that AMPK-C/A KI mice showed significant inhibition of exercise-induced angiogenesis (44%) via reducing angiogenic PGC1α and VEGF protein expression in SKM of T2D mice. In vitro, C2C12 skeletal muscles overexpressing SOD3 treated with palmitate (mimic T2D with exercise) induced AMPK-CysOH formation and VEGF secretion. Its conditioned media promoted angiogenic responses such as EC migration (1.8-fold) and tube formation (1.7-fold), which was inhibited by C2C12 cells overexpressing AMPK C/A mutant. Conclusion: Novel exercise-induced AMPK CysOH formation at Cys299/304 restores angiogenesis in SKM of T2D via SOD3-mediated H 2 O 2 , which may contribute to revascularization in diabetic PAD.
Abstract 18197: Relationship Between Donor Ejection Fraction and Left Ventricular Wall Thickness With Mortality Among Heart Transplants Recipients
Authors: Cesar R Zoni, Matthew Dean, Laurel Copeland, Julia Silverman, Christopher D Lemoine, Aviral Mahajan, Chittoor Sai Sudhakar, Yazhini Ravi
Journal: Circulation (2023)

Introduction: Limited availability of donor hearts contributes to significant mortality in patients waitlisted for heart transplantation (HTx). Donor hearts with reduced ejection fraction (EF) and left ventricular hypertrophy are considered to adversely affect long term HTX outcomes and are rejected. Objective: To determine the relationship of donor’s EF and left ventricular wall thickness (LVWT) with mortality in HTx recipients. Method: Retrospective analysis from The United Network for Organ Sharing (UNOS) registry. Adult HTx recipients with donor's EF and LVWT recorded from 2006 to 2022 were included. Study sample was grouped into four groups (Group 1 EF&gt;50% &amp; LVWT&lt;1.4cm, group 2 EF≤50% &amp; LVWT&lt;1.4cm, group 3 EF&gt;50% &amp; LVWT≥1.4cm, and group 4 EF≤50% &amp; LVWT≥1.4cm) according to donor characteristics. Primary end point: mortality (30 days, 1 year, and 5 years). Results: 21,012 patients were included, in which 19,205(91.4%) were in group 1, 898(4.3%) in group 2, 867(4.1%) in group 3, and 42(0.2%) in group 4. There were significant differences in baseline characteristics between the groups (Table 1). Unadjusted mortality was 6.3%, 6.0%, 6.0%, and 2.4% (p=0.86) at 30 days; 16.2%, 13.5%, 16.8%, and 7.3% (p=0.08) at 1 year; and 32.2%, 29.2%, 35.4%, and 29.0% (p=0.18) at 5 years, respectively (Table 1 and Figure 1). Neither adjusted mortality was different across the groups (Table 2). Conclusion: There were no significant differences in recipient mortality in different groups based on donor EF and LVWT. Expanding the donor selection criteria would allow for increase in the donor pool and assist in decreasing the mortality, while on the wait list for HTx.
Abstract 15544: Manipulating Oxygen-Releasing Levels and Oxidative Stress to Enhance Viability and Functionality of Human Pluripotent Stem Cell-Derived Cardiomyocytes for Myocardial Infarction Therapy
Authors: Xingyu He, Jialiang Liang, Wei Huang, Christian Paul, Suchandrima Dutta, Yi-gang Wang
Journal: Circulation (2023)

Introduction: Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) hold great promise for myocardial infarction (MI) treatment. Although O 2 -releasing engineering approaches have been developed to enhance stem cell engraftment, a significant gap persists in knowledge regarding the oxidative stress controlling viability and functionality of hPSC-CMs. Hypothesis: Preconditioning hPSC-CMs with appropriate oxidative levels will enhance their adaptation and engraftment in the infarcted heart. Aims: To develop a novel system that produces a controlled release of O 2 to supply engineered heart tissue for regenerative therapies. Methods: An O 2 -releasing hydrogel system (ORHS) was engineered using peroxides (sodium percarbonate) and antioxidants (β-carotene) encapsulated in PLGA-based particles. The effect of ORHS on hPSC-CMs was evaluated through oxidative stress assays, cell viability assessments, and contractility measurements. RNA-seq profiling was performed to analyze the gene expression of hPSC-CMs in response to ORHS. After implantation of ORHS-hPSC-CMs in infarcted hearts of immunodeficient mice, heart functions were monitored with echocardiography. Implanted cell engraftment was assessed using in vivo imaging systems and immunostaining. Results: The dissolved O 2 levels were increased in ORHS for 7 days, while the oxidative stress was minimized by β-carotene. The optimal ORHS significantly enhanced the viability and mitigated cell death of hPSC-CMs under hypoxic stress conditions. ORHS also enhanced cell contractility and improved calcium signaling in hPSC-CMs. Genes related to maturation and functionality (such as TNNT2, TNNI3, GJA1, and RYR2) were upregulated by ORHS in hPSC-CMs. Implantation of ORHS-hPSC-CMs for 4 weeks resulted in improved ejection fraction, reduced ventricular remodeling, alleviated infarct size, and scar formation. Furthermore, the engraftment and survival of hPSC-CMs were significantly increased by ORHS compared to control hydrogels, as demonstrated by luciferase reporter assays and troponin immunostaining with TUNEL. Conclusion: The development of ORHS offers a promising approach for inducing oxidative preconditioning and achieving enhanced regenerative outcomes of hPSC-CMs.
Abstract 15057: miR-132 Inhibitor CDR 132L Attenuates Cardiac Remodeling by Exhibiting Anti-Fibrotic Effects
Authors: Sandor Batkai, Celina Genschel, Janika Viereck, Steffen Rump, Wilfried Hauke, Mariann Gyongyosi, Denise Traxler, Rabea Hinkel, Christian Kupatt, Arthur A Levin, Thomas Thum
Journal: Circulation (2023)

Introduction: Increased cardiac expression levels of miRNA miR-132 have been associated with pathological cardiac remodeling including cardiac fibrosis. As a selective inhibitor for miR-132, the synthetic antisense oligonucleotide CDR132L, is capable to reverse cellular pathology and restore normal heart function. Pharmacological inhibition of miR-132 as well as genetic knockout has been shown to protect mice from transverse aortic constriction induced cardiac remodeling including interstitial fibrosis. Methods and Results: Treatment effects of CDR132L were investigated in several different pig models of ischemic and non-ischemic heart failure (HF) with the aim to further elucidate CDR132L’s mode of action and confirm species-independent effects on fibrotic remodeling. In a pig model of subacute post myocardial infarction (MI) induced HF, CDR132L was administered on day 3 and day 28 by intravenous (IV) or intracoronary (IC) infusion at doses of 1, 5 and 10 mg/kg and followed until day 56. In a chronic post-MI HF large animal model, beneficial effects were confirmed in a 6-month study comparing 5 monthly and 3 monthly repeated IV administrations of 5 mg/kg CDR132L starting one month post-MI. Further, CDR132L was tested in a porcine model of percutaneous aortic constriction by implantation of a reduction stent in the thoracic aorta and two IC injections of CDR132L on day 0 and day 28 followed for 56 days. As part of the pharmacodynamic analyses in these models, paraffin sections of cardiac tissue from the left ventricular remote region were stained with picrosirius red (PSR) and fibrosis was assessed based on collagen quantity. Analysis of fibrosis in PSR-staining revealed that the degree of interstitial fibrosis was significantly reduced in CDR132L treatment groups compared to placebo between 22% and 61%. Moreover, results of the first-in-human safety and tolerability study of CDR132L in patients with stable HF of ischemic origin (NCT04045405) showed encouraging positive trends for relevant cardiac fibrosis biomarkers. Conclusion: By blocking aberrant miR-132 expression, CDR132L is capable to halt and reverse pathological cardiac remodeling partly due to its anti-fibrotic effects.
Abstract 18676: Aneurysmectomy or No Aneurysmectomy - An Unknown Heart Failure Terrain
Authors: Mouna Penmetsa, Mai Badr, Vidya Nadig, Peter Vlismas, Andrew Scatola
Journal: Circulation (2023)

Case Report: A 40-year male with a history of traumatic inferoapical ventricular septal rupture after a motor vehicle accident status post patch repair and left ventricular thrombus on Rivaroxaban presented to the ED with hemoptysis. The patient on arrival was hemodynamically stable. CTA revealed a new 6.9 cm left ventricular pseudoaneurysm and an echocardiogram revealed an EF of 30% with a pseudoaneurysm involving the entire distal septum, lateral wall, and apex and a ventricular septal rupture into the intraventricular septum. Cardiac MRI revealed a pseudoaneurysm from the inferoseptal wall measuring 9.6 x 6.9 x 10.0 cm and a stroke volume of 123 mL. A right heart catheterization revealed no evidence of left-to-right shunting. Given heart failure with reduced ejection fraction in the setting of a pseudoaneurysm and the complexity of aneurysm repair, advanced heart failure and cardiothoracic surgery teams were consulted for conventional surgical and transplant evaluation. Due to social barriers, the patient was declined from transplant and ultimately proceeded with patch repair. Intraoperative echocardiography revealed a post-operative EF of 25%. Discussion: This case highlights the need for further data on pseudoaneurysms that are confounded with concurrent heart failure. For this patient, the concerns were for adequate stroke volume given the extent of the pseudoaneurysm and whether improvement in systolic function could be seen with repair or result in further decline. It was postulated that surgical repair would raise his effective stroke volume, and thus improve cardiac function. Postoperative EF changes could have been further explained by myocardial stunning during anesthesia or rapid changes in end-diastolic volume with aneurysmectomy altering Frank-Starling hemodynamics. With isolated case report data, further aneurysmectomy outcome characterization is thus imperative to guide advanced heart failure treatment and improve patient mortality.
Abstract 16715: Rare or Disregarded; A Case of Autoimmune Myopathy
Authors: Maryam Barkhordarian, Mark Grijalva, Amer Jarri, Anna Belyayeva, Simcha Weissman
Journal: Circulation (2023)

Introduction: Statin-induced myopathy can present with symptoms ranging from mild myalgia to significant muscle weakness. This case report highlights how statin-induced autoimmune myopathy often goes undiagnosed. Case Presentation: We present a 69 year old male with a past medical history of coronary artery disease who presented with myalgia and progressive proximal muscle weakness for 2 months. On admission, creatinine kinase (CK) level was noted to be elevated at 8323 u/L. Atorvastatin was held on admission and the patient received intravenous (IV) fluid as treatment for presumed rhabdomyolysis. Although CK was trending down, the patient did not show any significant improvement in muscle weakness or myalgia. At this point, myositis was suspected, so a myositis panel including anti-HMG Co-A Reductase antibody was ordered and the patient was started on IV steroids. Anti-HMG Co-A Reductase antibody was positive and the rest of myopathy workup was negative; meanwhile, the patient's muscle weakness significantly improved. The patient was discharged on a methylprednisolone with close outpatient rheumatology follow-up. Discussion: Drug-induced rhabdomyolysis is one of many causes of myalgia. It is crucial to review a patient’s medication list and discontinue any possible medications that are possible offenders. Statin-induced myopathy should also be suspected when typical treatment for rhabdomyolysis is failing. Statin induced autoimmune myopathy is associated with muscle weakness, elevated CK and a positive anti-HMG Co-A Reductase antibody, which requires discontinuation of Statin and initiation of immunosuppressive therapy. Conclusions: This case report highlights the importance of early identification and management of statin-induced autoimmune myopathy as a possible differential diagnosis in patients with muscle weakness, elevated CK levels while on statin therapy who do not respond to IV fluid alone.
Abstract 17053: Impact of Sodium-Glucose Cotransporter-2 Inhibitors on Mortality in Hypertrophic Cardiomyopathy: A Retrospective Study
Authors: Amro Aglan, Ayman Fath, Abdullah Eldaly, Jason Phillips, Allen S Anderson, Barry J Maron, Martin Maron, Ethan J Rowin
Journal: Circulation (2023)

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been demonstrated to improve outcomes in congestive heart failure (HF). However, their effect in hypertrophic cardiomyopathy (HCM) is unknown. Research Question: Can SGLT2i improve clinical outcomes in HCM patients? Methods: Using TriNetX Global Research Network from March 2013 to February 2021, patients diagnosed with HCM (ICD-10 codes I42.1, I42.2) were identified and categorized into 2 groups: those on SGLT2i vs. those who are not. To avoid inclusion of other causes of left ventricular hypertrophy, patients with aortic stenosis or systemic hypertension were excluded. Propensity score matching (PSM) was used to limit confounders. Primary outcome was all-cause mortality and secondary outcomes were HF exacerbation, all-cause hospitalization, and documented cardiovascular symptoms (chest pain, dyspnea, palpitations, or leg edema) over a 2-year follow-up period. Results: A total of 27,561 HCM patients were identified; 408 (1.5%) on SGLT2i and 27,153 (98.5%) were not. Patients on SGLT2i were older (55 ± 15 vs. 48 ± 19, p&lt;0.01) and had more comorbidities, including a nearly 6-fold higher prevalence of diabetes mellitus (44% vs. 7%, p&lt;0.01) and congestive HF (65% vs. 10%, p&lt;0.01). After PSM, each group consisted of 355 patients. HCM patients on SGLT2i had lower rates of all-cause mortality (OR 0.22 [95% CI: 0.12, 0.39]; p&lt;0.01), hospitalizations (OR 0.72 [95% CI: 0.53, 0.98]; p=0.04), and cardiovascular symptoms (OR 0.71 [95% CI: 0.52, 0.97]; p=0.029) when compared to patients not on SGLT2i. There was no statistical difference in the rate of HF exacerbation (OR 0.82 [95% CI: 0.54, 1.24]; p=0.3). Conclusion: In this large dataset, SGLT2i use in a select subset of HCM patients was associated with improved survival, less hospitalizations, and fewer cardiovascular symptoms. These data support future randomized trials to evaluate the efficacy and safety of SGLT2i in more diverse HCM patient populations.
Abstract 17256: Perturbations of Tryptophan Catabolism Through the Kynurenine Pathway Are Associated With Prolonged Mechanical Ventilation and Length of Stay After Stage 2 Palliation for Single Ventricle Heart Disease
Authors: Jennifer Romanowicz, Ludmila Khailova, Sierra Niemiec, Max B Mitchell, Gareth J Morgan, Mark Twite, Michael V DiMaria, Jelena Klawitter, Jesse A Davidson, Benjamin S Frank
Journal: Circulation (2023)

Background: Infants with single ventricle heart disease (SVHD) have perturbed kynurenine pathway (KP) function prior to stage 2 palliation. Buildup of kynurenic acid—a byproduct of this pathway—is linked to worse outcomes post stage 2. To date, perturbations along the entire KP have not been delineated in SVHD infants at the time of stage 2 operation. Methods: This is a single center prospective cohort study of 75 infants with SVHD undergoing stage 2 palliation and 50 controls. Targeted analysis of KP metabolites was performed on serum samples via tandem mass spectroscopy prior to stage 2 (baseline) and post-operatively at 2, 24, and 48 hours. Results: Of the 9 KP metabolites, 7 were different between controls and SVHD at baseline (Figure 1A). SVHD infants had lower tryptophan and serotonin; and higher kynurenic acid, 3-hydroxykynurenine, anthranilic acid, picolinic acid, and 3-hydroxyanthranilic acid. After stage 2, there were time related changes in all KP metabolites except tryptophan (Figure 1B). Metabolite concentrations at baseline and 2 hours post-op were poorly correlated with outcomes. At 24 hours, decreases in tryptophan and serotonin along with elevations in kynurenine, kynurenic acid, 3-hydroxykynurine, and quinolinic acid concentrations correlated with outcomes (Figure 1C). At 48 hours, kynurenic acid remained positively correlated with all 3 outcomes (length of stay, hypoxia burden, and intubation length). Conclusions: We demonstrated numerous perturbations in the KP pathway at baseline in SVHD infants compared to controls. We also profiled the trajectory of each metabolite over the 48 hours post stage 2. The link between KP intermediates and poor outcomes post-operatively—but not at baseline—demonstrates that the acute, peri-operative changes in tryptophan catabolism in response to cardiopulmonary bypass are more important to tolerating new stage 2 physiology than chronic changes during the interstage period.