tbuckley/cabot-search huggingface dataset:
Abstract 4147316: Utilization of Palliative Care for Patients Living with Long-Term (LT) LVAD Therapy
Authors: Marc El Khoury, Patrick Creechan, Richa Gupta, Michael Hockstein, Victor Avila-Quintero, Jose Flores, Keki Balsara, Kelley Anderson, Hunter Groninger, Farooq Sheikh, Anirudh Rao
Journal: Circulation (2024)

Background: Outpatient palliative care has been associated with improved health-related quality-of-life (HRQoL) in patients with heart failure. However, there is limited understanding of its utilization among patients with long-term left ventricular assist device (LT-LVAD) therapy. The prevalence of LVAD implantation as long-term therapy has increased over the past decade; these patients may particularly benefit from outpatient palliative care. Objective: To identify the predictors of outpatient palliative care utilization in a sample of LT-LVAD patients from a high-volume LVAD center. Methods: This retrospective chart review analyzed data from 270 patients who received LVAD as long-term therapy between January 1, 2017, and December 30, 2021, and were supported on LVAD therapy for at least two years. Patients who received heart transplantation prior to the study end-date were excluded. Logistic regression models were used to estimate the odds of receiving outpatient palliative care (with or without inpatient palliative care) versus receiving inpatient palliative care alone. Results: Among 270 patients, the mean age was 62 years (+/- 12), 74.2% were male, 79.0% Black and 17.3% White. By device: 77.4% received HeartMate 3™ (HM3), 19.6% HVAD™ LVAD, 3.0% HeartMate II™. Patients lived an average of 4 years (+/- 1) post-implantation. The mean number of hospitalizations from implantation to death or end-of-study was 7.85 (+/- 7.04). 180 patients received inpatient palliative care consultation alone; 90 patients received at least one outpatient palliative care visit. Black patients had increased odds of receiving outpatient palliative care compared to White patients (OR 2.27, P=0.040). For each additional hospitalization a patient experienced, the odds of receiving outpatient palliative care increased (OR 1.06, P=0.002). Patients with HVAD™ LVAD were less likely to receive outpatient palliative care than those with HM3 (OR 0.45, P=0.029). Conclusion: In this large cohort of patients supported on LT-LVAD therapy, Black patients were more likely to receive outpatient palliative care than White patients. More frequent hospitalizations and LVAD type were associated with an increased likelihood of outpatient palliative care visits. Future studies should explore the factors contributing to these differences to better understand and enhance palliative care utilization for all patients on LT-LVAD therapy.
Abstract 4146837: Risk of Cardiac Events of New-generation versus Old-generation Bruton Tyrosine Kinase Inhibitors in Patients with Hematological Malignancies: A Systematic Review and Meta-analysis of RCTs
Authors: Buena Aziri, Edin Begic, Catalina Herran-Fonseca, Laura Jekov, Ana Gabriela Ponte Farias, Carlotta Persaud, Norma Gamarra, Maysa Vilbert, Fahad Alabbas
Journal: Circulation (2024)

Background: Bruton Tyrosine Kinase inhibitors (BTKi) are targeted therapies that have demonstrated promising results in the treatment of hematological malignancies; however, they are associated with adverse cardiac events. Direct comparisons of the cardiotoxic profile between old-generation and new-generation BTKi are limited. Research Question: Are novel BTKi associated with a lower incidence of cardiac adverse events compared with ibrutinib? Aims: We aimed to perform a systematic review and meta-analysis of cardiac events from studies comparing new-generation BTKi versus ibrutinib in patients with hematological malignancies. Methods: We searched PubMed, Embase, and Cochrane Library for studies comparing any new-generation BTKi with ibrutinib in patients with hematological malignancies. Outcomes included 1) risk of cardiac events; 2) atrial fibrillation (AF); 3) rate of treatment discontinuations due to AF; and 4) hypertension. We pooled risk ratios (RR) with 95% confidence intervals (CI). Statistical analysis was performed using R software 4.3.1, under a random-effects model. Heterogeneity was assessed using I 2 statistics. Results: We included four randomized controlled trials with 1905 patients, of whom 957 (50%) received new-generation BTKi. Age ranged from 28 to 90 years, with 1337 (70%) male patients. Prior lines of systemic therapy ranged from none to 12. Overall cardiac events were significantly lower in patients who received novel BTKi compared with those who received ibrutinib (RR 0.75; 95% CI 0.63 to 0.90; p=0.002; I 2 =0%; Fig.1A). New-generation BTKis were associated with a statistically significant reduction in the risk of AF (RR 0.48; 95% 0.35 to 0.64; p&lt;0.001; I2=0% Fig.1B) and treatment discontinuation due to AF (RR 0.07; 95% CI 0.01 to 0.34; p=0.001; I 2 =0%), compared with ibrutinib. However, there was no statistically significant reduction in the risk of hypertension with novel BTKi relative to ibrutinib (RR 0.58; 95% CI 0.34 to 1.01; p=0.053; I 2 =81%). Conclusion: Our findings suggest that treatment with new-generation BTKi is associated with a significant reduction in the risk of cardiac events, AF, and AF-related treatment discontinuation compared with the old-generation BTKi.
Abstract 4146841: Unsupervised Agglomerative Cluster Phenotyping of Young Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention
Authors: Muhammad Haisum Maqsood, Rody Bou Chaaya, Kershaw Patel, Sahar Samimi, Taha Hatab, Fatima Qamar, Chloe Kharsa, Sachin Goel, alpesh shah, Neal Kleiman, Safi Khan
Journal: Circulation (2024)

Introduction: Young patients with acute coronary syndrome (ACS) exhibit diverse demographic, clinical and angiographic characteristics. Hypothesis: We hypothesized that unsupervised machine learning (ML) can identify phenotypic clusters and predict the prognosis among young patients with ACS who undergo percutaneous coronary intervention (PCI). Methods: We used the Houston Methodist Young-ACS PCI registry (2010-2022) and performed agglomerative clustering to analyze demographic, clinical and angiographic variables among young patients (≤50 years) treated with PCI for ACS. Results: Among 633 patients, cluster analysis identified three distinct phenotypes. Low risk (n=273) exhibited lowest proportions of heart failure (HF: 10.3%) and peripheral arterial disease (PAD): 5.9%), normal left ventricular ejection fraction (LVEF) (median =0.60) and shorter median culprit vessel stent length (16 mm). Moderate risk (n=101) was characterized by moderate rates of diabetes (36.6%), hypertension (77.2%), prior myocardial infarction (16.8%) and prior PCI (18.8%). High risk (n=78) had highest proportion of diabetes (67.9%), hypertension (93.6%), HF (65.4%), PAD (17.9%), prior MI (41.0%), prior PCI (46.2%), the lowest median LVEF (0.3) and the most frequent use of mechanical circulatory device (5.1%). All-cause mortality differed significantly ( Figure ), with high-risk cluster showing a four-fold increase in all-cause mortality (HR: 4.50 [1.68-12.1]). There was no significant difference in mortality between moderate and low-risk clusters (HR: 1.52 [0.44-5.19]). Conclusions: Through unsupervised ML, we identified three distinct phenotypic clusters among young patients with ACS treated with PCI, each exhibiting varying degrees of comorbidity burden and allowing identification of patients with high mortality risk, thus underscoring the potential for phenotype-guided therapeutic approaches.
Abstract 4147332: Echocardiographic Risk Prediction of Outcomes in Acutely Ill Pulmonary Arterial Hypertension Patients
Authors: Jasmine Malhi, Hoda Mombeini, Vivek Jani, Mario Naranjo, Valentina Mercurio, Ryan Osgueritchian, Hussein Hassan, Steven Hsu, Catherine Simpson, Rachel Damico, Todd Kolb, Stephen Mathai, Paul Hassoun, Monica Mukherjee
Journal: Circulation (2024)

Background: Despite advancements in pulmonary arterial hypertension (PAH) management both in-hospital and long-term mortality remain high for those admitted to the ICU. Aims: We sought to identify echocardiographic predictors of outcomes and to develop a straightforward risk prediction score to predict one-year mortality in ICU-admitted PAH patients. Methods: This single-center, retrospective study examines adult PAH patients hospitalized in the JHH ICU from January 2010 to December 2020. Echocardiographic indices were collected and associated with outcomes using Cox proportional hazards (CPH) modeling to predict one-year mortality. Using these indices as well as clinical and lab data, a machine learning (ML) prediction model, Random Survival Forest (RSF), was trained and evaluated with a time-varying area under the curve (AUC). Results: Out of 102 PAH patients, 77 had complete echocardiograms at index hospitalization. Baseline characteristics are presented in Table 1. Right ventricular (RV) dilatation, RV contractile dysfunction (impaired TAPSE, FAC, and RVFWLS), more positive RA conduit strain, and RV-pulmonary artery (PA) uncoupling were associated with increased one-year mortality after adjusting for age, sex, race, and functional class (Figure1A). Kaplan-Meier survival curves revealed that TAPSE, TAPSE/PASP, RVFWLS, and RVFWLS/PASP have significant prognostic discriminative ability at optimal thresholds of 13 mm, 15 mm/mmHg, -9.5%, and 15%/mmHg, respectively. Our best ML RSF model achieved a mean time-varying AUC of 0.73 (Figure1B), with the top five predictors being estimated 4-chamber LV end-diastolic volume, FAC, echo-derived PASP, RVFWLS, and echo-estimated pulmonary vascular resistance (Figure1C-D). Conclusion: Echocardiographic right heart functional indices are associated with one-year mortality in ICU-admitted PAH patients. Employing these parameters in an ML model was predictive of adverse clinical outcomes.
Abstract 4146888: Safety report from a remote disease management program to improve sodium glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonist prescribing in Type 2 diabetes
Authors: Shahzad Hassan, Lee-Shing Chang, Dan Gabovitch, Gretchen Stern, Jacqueline Chasse, David Zelle, Caitlin Colling, Samuel Aronson, Christian Figueroa, Emma Collins, Ryan Ruggiero, Thomas Gaziano, Jorge Plutzky, Christopher Cannon, Deborah Wexler, Benjamin Scirica, Alexander Blood
Journal: Circulation (2024)

Introduction: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) offer cardiovascular (CV) and kidney protective effects in patients with Type 2 DM (T2DM). Despite the benefits, these medications are underutilized due to various barriers. Remote management programs present a scalable solution to improve uptake of these medications in accordance with guidelines. However, safety concerns may limit the adoption of such programs. We report adverse effects (AEs) and safety outcomes in participants who initiated either medication class within a remote program. Methods: The Diabetes Remote Intervention to improve the use of Evidence-based medications (DRIVE) Program was a randomized study conducted at Mass General Brigham (MGB), tertiary care medical center. The aim of study was to initiate SGLT2i or GLP-1 RA in T2DM patients with or at higher risk of CV and/or kidney complications. A total of 200 participants were enrolled in 2-months of Education-first or Simultaneous Education and medications initiation arm, with 106 starting SGLT2i or GLP-1 RA treatment within six months of enrollment. Study staff regularly contacted participants who were initiated on either medication to assess AEs and safety outcomes. Results: Of 68 participants who started on an SGLT2i, 35 (51.5%) experienced any AE, 8 (11.8%) had a genitourinary AE and 7 (10.3%) experienced an AE that led to discontinuation of drug. Of 40 participants who started on a GLP-1 RA, 22 (55.0%) experienced any AE, 19 (47.5%) had a gastrointestinal AE and 4 (10.0%) experienced an AE that led to discontinuation of drug. Nearly all medication-related AEs were managed by DRIVE program clinicians independently or in collaboration with participant’s outpatient clinical team. Conclusion: The DRIVE program safely initiated and managed SGLT2i or GLP-1 RA treatment in participants. The rates of AEs observed were comparable to those reported in clinical trials, supporting the scalability, effectiveness, and safety of remote initiation and management of these drugs. Furthermore, AEs from these medications can be successfully managed remotely by a clinical team in conjunction with participants’ primary providers.
Abstract 4147352: Donation After Circulatory Death Is Associated with Increased Morbidity and Mortality in Heart Transplant Patients Supported by Mechanical Circulatory Support Devices
Authors: Melinda Song, Amy Fiedler, Jason Smith, Liviu Klein, Mandar Aras
Journal: Circulation (2024)

Background: In recent years, both mechanical circulatory support devices (MCSD) and grafts from donation after circulatory death (DCD) are increasingly utilized for patients undergoing heart transplant. Multiple studies have demonstrated no difference in outcomes for DCD recipients compared to donation after brain death (DBD). To date, no study has examined whether outcomes remain similar among patients supported with MCSD pre-transplant. Methods: Using the United Network for Organ Sharing database, adult patients who underwent single-organ heart transplant from 12/1/2019 to 12/31/2023 were identified. MCSD included extracorporeal membrane oxygenation (ECMO), intra-aortic balloon pump (IABP), Impella, and durable ventricular assist devices (VAD). Results: Among 12131 patients as defined above, 1059 (8.7%) received DCD and 11072 (91.3%) received DBD grafts. Of these, 557 (52.6%) DCD recipients and 7315 (66.1%) DBD recipients were supported with at least one MCSD pre-transplant. Recipients on ECMO or IABP were more likely to receive DBD grafts, whereas those with durable VADs were more likely to receive DCD grafts (Figure 1). There was no significant difference in DCD vs. DBD selection for patients supported by Impella (4.06% vs. 4.85%, p=0.087). In the MCSD population, DCD recipients had a 30% increased risk of mortality compared to DBD recipients (95% confidence interval: 1% to 69%; Figure 2). Compared to DBD recipients, DCD recipients had higher rates of new dialysis post-transplant (17.4% vs. 14.0%, p=0.031) and higher rates of re-transplant (1.3% vs. 0.4%, p=0.016). Mean graft left ventricular ejection fraction at 1 year did not differ significantly between DCD vs. DBD recipients (59% vs. 60%, p=0.308). Conclusions: For patients supported by MCSD pre-transplant, receiving a DCD graft is associated with higher morbidity and mortality. Clinicians should proceed with caution in selecting DCD donors for this population.
Abstract 4146828: Downregulation of ADAR1 Attenuates Hypothermic Cardioprotection in Aged Donor Hearts During Transplantation
Authors: Dunpeng Cai, Shiyou Chen
Journal: Circulation (2024)

Heart transplantation remains a vital treatment for end-stage heart failure, yet the scarcity of suitable donor hearts makes the treatment unavailable to many patients in critical need. Aged donor hearts, despite their availability, exhibit increased primary graft dysfunction and decreased survival rates post-transplantation. Addressing this critical barrier could potentially improve post-transplant outcomes and make older donor hearts a viable option. In this study, using a mouse heterotopic heart transplant model, we first confirmed that hypothermic cardioprotection was significantly impaired in aged donor hearts but preserved in young donor hearts. RNA-Seq analyses revealed down-regulation of RNA editing activity along with exacerbated Endoplasmic reticulum stress (ER stress) and increased unfolded protein response (UPR) activity in aged donor hearts post-transplantation. Supplementing cardioplegic solution with rapamycin, an inhibitor of both ER stress and UPR, relieved graft heart dysfunction in aged mice, indicating that ER stress and UPR are responsible for this dysfunction. Furthermore, we found that Adenosine Deaminase Acting on RNA-1 (ADAR1) was downregulated in aged donor hearts post-transplantation in both our mouse model and in human patients. Importantly, ADAR1 deficiency in young donor hearts abolished hypothermic cardioprotection, leading to increased UPR activity, ER stress, and cellular senescence. Conversely, overexpression of ADAR1 in aged donor hearts by a novel PEG-based nanoparticle delivery in cardioplegic solution enhanced hypothermic cardioprotection by decreasing UPR activity, ER stress, and cellular senescence. Mechanistically, ADAR1 controls the expression of p16. In aged donor hearts, ADAR1 downregulation caused an increased expression of p16, which competed for its binding with CDK4/6, leading to a decreased phosphorylation of Rb and subsequent cellular senescence. These findings suggest that ADAR1-associated RNA editing activities play a crucial role in the hypothermic cardioprotection of donor hearts. Supplementing cardioplegic solutions with nanoparticles that enhance ADAR1 activity or modulate ER stress responses may provide a promising therapeutic strategy to improve the viability and/or function of aged donor hearts in transplantation.
Abstract 4147247: A Deep Learning Topic Analysis Approach for Enhancing Risk Assessment in Heart Failure Using Unstructured Clinical Notes
Authors: Philip Adejumo, Aline Pedroso Camargos, Rohan Khera
Journal: Circulation (2024)

Background: Assessing clinical complexity in heart failure (HF) patients is essential for effective resource allocation. Despite notable limitations, CMS currently uses administrative claims to estimate complexity and determine provider payments. Unstructured clinical notes contain valuable patient information that can enhance risk assessment. We introduce a novel deep-learning approach that identifies clinically significant features from notes to improve risk assessment in HF. Methods: We identified all individuals with hospitalizations for HF in a large, diverse health system and defined CMS HF comorbidities using ICD codes. In parallel, we extracted clinical notes from these encounters to determine information relevant to the same conditions using a novel natural language processing-based topic modeling approach. We digitized all notes into a vector space using a previously trained embedding model (NV-embed) with learned contextual word associations. We projected the descriptions of CMS ICD-code-based risk factor categories into the embedding and used cosine similarity to identify whether notes provided additional information. We used logistic regression models for 30-day readmission and 30-day and 1-year mortality to evaluate the predictive performance of the approaches. Results: We identified 40,604 HF hospitalizations, with 30-day and 1-year mortality rates of 6.4% and 18.2%, and 30-day readmission rate of 23.3%. Clinical notes of those with vs without a code-based comorbidity had the information identifiable on topics (cosine similarity, 0.73 vs 0.57). Among those without coded conditions, notes varied substantially in information corresponding to the topic (range of coefficient of variation, 0.21-0.50). Models using note-defined topics as predictors consistently outperformed those using CMS risk scores, with higher AUROCs for 30-day mortality (0.81 vs 0.63), 1-year mortality (0.85 vs 0.64), and 30-day readmissions (0.78 vs 0.59). The average net reclassification index was 0.37, indicating improved risk stratification using information from notes vs structured CMS risk scores. Conclusion: A novel deep-learning approach applied to unstructured clinical notes more accurately identifies conditions of interest, with the models based on these features significantly outperforming the current CMS risk-adjustment models for post-hospitalization events. This has important implications for defining the next generation of tools for hospital profiling for HF care.
Abstract 4146689: Mavacamten: Real-World Experience from 22 Months of the Risk Evaluation and Mitigation Strategy (REMS) Program
Authors: Milind Desai, Dewey Seto, Michael Cheung, Michele Coiro, Niki Patel, Arnaud Bastien, Jeffrey Lockman, Sonia Afsari, Matthew Martinez
Journal: Circulation (2024)

Introduction: Mavacamten is a cardiac myosin inhibitor approved by the US FDA for the treatment of adults with symptomatic New York Heart Association class II-III obstructive hypertrophic cardiomyopathy to improve functional capacity and symptoms. Under the risk evaluation and mitigation strategy (REMS) program, patients taking mavacamten are required to be monitored for development of systolic heart failure (HF), with interruption if left ventricular ejection fraction (LVEF) decreases to &lt;50%. Aims: We report updated results from the mavacamten REMS database (28-Apr-2022 to 27-Feb-2024), including safety data for patients treated for ≥1 year. Methods: Data on health care providers and pharmacy certification, patient monitoring (including health status forms and echocardiograms), and screening for drug interactions prior to each dispense were collected. Results: Of 6,299 patients who received ≥1 dose of mavacamten, 60.0% were women; ages were &lt;18 (0.1%), 18-40 (6.3%), 41-60 (29.0%), and ≥61 years (64.6%). Of 5,573 patients with submitted health status forms as of 27-Feb-2024, 256 (4.6%; Figure A) experienced a decrease in LVEF to &lt;50% and 71 (1.3%) experienced HF requiring hospitalization (HFH). On the 29,111 status forms, LVEF &lt;50% was reported on 276 (0.9%) and HFH was reported on 86 (0.3%). Of 1,929 patients with ≥1 year of treatment (Figure B), 78 (4.04%) had an LVEF reduction to &lt;50% and 4 (0.21%) experienced LVEF &lt;50% + HFH (with potential confounders like atrial fibrillation) but later resumed treatment. A planned dosing analysis will provide further insights. Of 52,432 drug interaction checklists completed, 130 (0.25%) resulted in mavacamten dose reduction and 167 (0.32%) resulted in discontinuation of a concurrent medication. Conclusions: In &gt;6,000 patients during the first 22 months of the REMS Program for mavacamten, the need for temporary interruption for LVEF &lt;50% was very low, including for patients on therapy ≥1 year, with even fewer LVEF reductions associated with HFH. Additionally, a low proportion of patients had potential drug-drug interactions, with a low number requiring a mavacamten dose reduction. The data suggest favorable real-world experience with mavacamten, confirmed by REMS oversight.