tbuckley/cabot-search huggingface dataset:
Abstract 4139192: Remote monitoring platform improves communication and clinical decision making for pediatric interstage healthcare team members
Authors: Lori Erickson, Amy Ricketts, Melissa ELLIOTT
Journal: Circulation (2024)

Background: Asynchronous remote patient monitoring (RPM) is increasingly common in healthcare models for infants with congenital heart disease (CHD). Using a downloadable mobile application with a software platform like CHAMP App ® allows parents to proactively engage in data entry, providing pediatric healthcare teams (HCT) timely information without relying solely on parent messaging or calls. Research Question: How does the use of RPM impact family communication and clinical decision-making experiences for HCTs? Goals: To identify the HCT’s experience through a secondary review of the CHAMP Cardiac Repository, using parent-entered interstage data from home for infants with CHD. Methods: This retrospective multi-institution cohort (Table 1) spanned from 5/2019-8/2023, collecting HCTs feedback via Likert responses (Table 2) about experiences with infant monitoring endpoint, which were analyzed in SPSS. Results: Response rates of 75.8% (493/650) were achieved across 10 pediatric cardiac care centers. HCTs reported improved communication (4.5 + .77) and clinical decision-making with video reviews (4.47 + .79). Parents' data engagement averaged 268 + 195.3 total points (oxygen saturation, weights, and/or videos) per infant. Higher engagement correlated with better HCT communication (p &lt;.001) and decision-making (p &lt;.0001), both with small effect sizes. Improved clinical decision-making was noted in families who used study-provided iPads for video recordings (mean score 4.63 ± 0.84) compared to those using personal devices (mean score 4.42 ± 0.734, p = .03), with 69.2% using personal devices. Conclusions: In this modern cohort, families engaged well with data entry through a remote monitoring platform, and HCTs reported significant improvements in communication with families for their child’s data from home and clinical decision-making after reviewing videos. Future research should explore barriers to mobile data engagement and assess HCT preferences for video review.
Abstract 4146319: Racial Disparities and Driving Factors in the AHA's Life's Essential 8 Among American Adults: Insights from NHANES 2011-2020
Authors: Huanhuan Yang, Chenxi Huang, Kamil Faridi, Erica Spatz, Zhiui Li, Harlan Krumholz, Yuan Lu
Journal: Circulation (2024)

Backgrounds: The AHA introduced "Life's Essential 8" (LE8) in 2022 as a comprehensive metric to facilitate detailed tracking and management of cardiovascular health (CVH) at the population level. However, the racial/ethnic differences in LE8, how these differences change over time, and the driving factors of LE8 in each subgroup remain unclear. Methods: We utilized data from the continuous NHANES from 2011 to 2020 to examine racial disparities and driving factors in the AHA's LE8 among American adults. To ensure national representation, appropriate weights were applied. Survey-weighted and age-standardized trends in LE8 scores by racial and ethnic groups were analyzed using generalized linear models (GLMs). To identify the driving factors—specific metrics influencing the LE8 overall score—we calculated z-scores for all components. Then we used the spider chart to visualize the driving factors. Results: A total of 13,915 adult were included, of whom the mean age is 47.9 ± 0.37 years, 6,612 (47.55%) were women, 3,485 (14.63%) were Hispanics, 5,335 (69.74%) were non-Hispanic Whites, 3,464 (10.82%) were non-Hispanic Blacks, and 1,631 (4.81%) were Asians. From 2011-2020, the LE8 scores did not change significantly overall and across all racial groups (all p-trend &gt; 0.10, Figure 1 ). During the study period, racial/ethnic disparity persisted with Asian adults consistently having the highest LE8 scores and Black adults having the lowest scores. Notably, the lower LE8 scores in Black adults were primarily driven by lower scores of diet, blood pressure, and sleep health, whereas the higher LE8 scores in Asian adults primarily driven by higher scores of diet, nicotine exposure, and BMI. The LE8 scores in White adults were primarily driven by blood glucose and physical activity and the LE8 score in Hispanic adults were primarily driven by blood pressure ( Figure 2-A ). In 2017-2020 ( Figure 2-B ), Black adults had the lowest scores for all LE8 components, except for blood lipids. In contrast, Asian adults had the highest scores in diet, physical activity, nicotine exposure, and sleep health. Throughout the study period, the racial/ethnic disparity in LE8 score did not change significantly (all p &gt;0.10). Conclusion: We found persistent racial disparities in cardiovascular health among U.S. adults, with Black adults having the lowest LE8 scores in almost all components. The driving factors for LE8 scores varied by racial subgroups, emphasizing the need for targeted interventions.
Abstract 4146316: Venous Remodeling and Occlusion Accompany Arterial Pathology in Patients with Chronic Limb Threatening Ischemia
Authors: Jocelyn Beach, Navneet Narula, Elena Aikawa, Lucas Marinho, Mandy Turner, Cassandra Clift, Alan Morrison, Jagat Narula, Aruna Pradhan
Journal: Circulation (2024)

Background: Chronic limb threatening ischemia (CLTI) is defined as the presence of peripheral artery disease (PAD) in combination with rest pain or tissue loss and represents advanced arterial occlusive disease. Little is known about associated venous pathology as prior pathologic reports were limited to evaluation of maximally diseased arterial lesions. Objectives: To characterize arterial and venous histopathology in patients with CLTI. Methods: Tissue containing peripheral arteries and veins from the femoropopliteal to distal tibial arteries was harvested from 10 patients who underwent amputation for CLTI (Fig 1). Vessels were sectioned at 0.5 cm intervals, and histopathologic features were catalogued across 535 arterial and 493 venous sections. Results: Consistent with PAD, atherosclerotic lesions were more prevalent in proximal than distal arteries; 81.8% (27/33) femoropopliteal sections compared to 26.6% (134/502) of tibial sections. Severe stenosis (&gt;90%) was noted in 21.9% (117) of sections and was associated with atherosclerosis (pathological intimal thickening, fibroatheroma, fibrocalcific or fibro-osseous lesions) in 10.3% (12), luminal thrombi in 68.4% (80), or both in 21.4% (25) of arterial sections. In all patients and in 99.0% (488/493) of venous sections, irrespective of the degree of arterial luminal stenosis, adjacent large (≥1000µm) and small diameter veins revealed marked thickening of the vessel wall comprised of fibrosis and smooth muscle hyperplasia (Fig 2). While large veins retained luminal patency, small veins exhibited severe luminal stenosis or obliteration. Venous thrombosis was uncommon, occurring in 3.0% (15/493) of sections. Conclusions: Venous remodeling with stenosis and occlusion is highly prevalent and coincides with arterial disease pathology in patients with CLTI. This novel finding of previously underappreciated and severely altered venous pathology suggests a possible additional mechanism for limb ischemia in CLTI.
Abstract 4136996: Co-morbid Insomnia and Obstructive Sleep Apnea (COMISA) are Related to Incident Hypertension in a 20-Year Retrospective Cohort Study of 1.3 million Younger Men and Women Veterans: Associations by Sex
Authors: Allison Gaffey, ANDREY ZINCHUK, Henry Yaggi, cynthia brandt, Sally Haskell, Matthew Burg
Journal: Circulation (2024)

Introduction: Insomnia and obstructive sleep apnea (OSA) each increase risk for hypertension (HTN). Among older adults, there is a negative synergistic association of comorbid insomnia and OSA (i.e., COMISA) on incident cardiovascular disease (CVD) but it is unknown if this comorbidity is associated with HTN risk earlier in the lifespan. Research Questions: 1) Is COMISA associated with incident HTN among younger adults? 2) Do COMISA-HTN associations differ by sex? Hypotheses: We hypothesized that 1) COMISA would be associated with a greater risk of HTN than having no sleep disorder, 2) the hazard would be larger than for insomnia and OSA alone, and 3) distinct COMISA-HTN associations would be observed among men and women, respectively. Methods: Analyses included Veterans who enrolled in Veterans Health Administration (VA) care 2001-2021, a group selected because of its early adult age distribution. We merged administrative data, including outpatient and inpatient encounters, diagnoses, (ICD-9-CM/10 codes/dates) and pharmacy records. Veterans without demographic data, a history of other sleep disorders or CVD, or &lt;2 clinical encounters were excluded. Sleep disorders were defined by 1 inpatient or ≥2 outpatient encounters. HTN was defined by 1 inpatient or ≥2 outpatient encounters and/or ≥1 antihypertensive medication fill. Time-varying Cox proportional hazard models were adjusted for sociodemographic, behavioral/lifestyle, and clinical factors, and stratified analyses by sex. We used multiple imputation to address missing data. Results: Analyses included 1,293,165 Veterans (12% women; mean age 32.8) with an average follow-up of 7.6 years. Men with COMISA showed a 19% greater risk of HTN vs. no sleep diagnosis (95% CL: 1.17-1.20). Risks were slightly lower – but still significant – for men with only insomnia (HR:1.08 [95% CL: 1.06-1.09]) or only OSA (HR:1.15 [95% CL: 1.13-1.16]). Women with COMISA had a 21% greater risk of HTN vs. those without a sleep diagnosis (95% CL: 1.16-1.26), and those with insomnia (HR:1.15 [95% CL: 1.11-1.19]) or OSA (HR:1.13 [95% CL: 1.09-1.17]) showed a lower, though still significant risk. Conclusion: In this younger group, Veterans with COMISA had a 19-21% greater risk of HTN than without a disorder, and this risk was similar by sex and slightly higher than that attributable to insomnia or OSA alone. Increased identification of disordered sleep among younger adults should be a cardiovascular prevention priority.
Abstract 4139196: Long-term effectiveness and safety of mavacamten in a real-world, multi-center, global study: Preliminary results of COLLIGO-HCM from a diverse cohort in the United States
Authors: James Macnamara, Arnon Adler, Elad Maor, Rachel Bastiaenen, Matthew Gold, Ervant Maksabedian Hernandez, Xu Han, Patricia Schuler, Joel Salazar, Paula Orlandi, Leanne Li, Angel Pichardo, ozlem bilen
Journal: Circulation (2024)

Introduction: The mavaCamten ObservationaL evIdence Global cOnsortium in hypertrophic cardiomyopathy (COLLIGO-HCM; ClinicalTrials.gov ID NCT06372457) is a multinational, multicenter observational research initiative aiming to describe the real-world outcomes of mavacamten for the treatment of obstructive HCM. Aims: Describe the real-world effectiveness and safety of mavacamten, measured by echo measurements and NYHA class. Methods: This retrospective study used data from medical records from two participating HCM centers in the US. Patient-level data was extracted to assess the effectiveness and safety of mavacamten post-treatment initiation through 60 weeks. Patient characteristics and outcomes were described, including echocardiogram measurements, New York Heart Association (NYHA) functional class, and safety. Results: A total of 93 patients were treated with mavacamten (mean age 60.6 ± 13.9 years, 23.7% black, 57.0% female, and 77.4% NYHA class III at baseline) with a mean follow-up of 37.0 ± 28.1 weeks ( Table ). From baseline to week 60, 3 (3.2%) patients experienced temporary treatment discontinuation, and 3 (3.2%) discontinued mavacamten due to left ventricular ejection fraction (LVEF) &lt;50%. By week 12, 77.1% of patients had improved by ≥1 NYHA class. The percentage increased to 89.5% by week 24 and remained stable through week 60. Mean changes from baseline in resting and Valsalva left ventricular outflow tract gradients were 31.8 ± 32.8 and 57.3 ± 47.3 mmHg, respectively, at week 24, and remained similar through week 60. Mean change in LVEF from baseline was 4.1 ± 7.1% at week 12 and remained largely unchanged through week 60 (Figure) . Conclusions: This study demonstrated the early and sustained effectiveness of mavacamten with one of the longest follow-ups to date, in a real-world population with a higher racial diversity and disease burden than those in the clinical trials. This data further substantiates the effectiveness and safety profile of mavacamten.
Abstract Su804: Use of Machine Learning Models to Predict Neurologically Intact Survival for Advanced Age Adults Following Out-of-hospital Cardiac Arrest
Authors: Ryan Coute, Kameshwari Soundararajan, Dylana Adams, Brian Nathanson, Timothy Mader, Ryan Godwin, Ryan Melvin
Journal: Circulation (2024)

Background: We recently published a multivariable logistic regression model that successfully predicted neurologic outcomes in advanced age adults (≥ 65 years old) who achieve return of spontaneous circulation following out-of-hospital cardiac arrest (OHCA). Prior to externally validating this model, we sought to compare the predictive performance of our logistic regression model against common machine learning (ML) algorithms using the same dataset. Methods: We performed a retrospective observational analysis of the Cardiac Arrest Registry to Enhance Survival database from 2013-2021. All non-traumatic OHCA occurring in adults (≥65 years) who survived to hospital admission were included. The primary outcome measure was neurologically intact survival defined as a cerebral performance category (CPC) score of 1 or 2 at hospital discharge. Our original logistic regression model was compared to Boosted Trees and Decision Tree ML algorithms and assessed using accuracy, Area Under the Receiver Operating Characteristic Curve (AUC-ROC) and Area Under the Precision-Recall Curve (AUC-PR). The model variables included age, gender, race/ethnicity, location, witnessed status, who initiated cardiopulmonary resuscitation, whether an automated external defibrillator was applied prior to emergency medical services arrival, and first monitored rhythm. Results: A total of 83,561 OHCA were included. Median age was 75 years (IQR 69-82), 58.9% were male, 53% were White, 67% experienced an OHCA at home, 52% were witnessed by a bystander, 44% received bystander CPR, and 34% were found in shockable rhythm. Neurologically intact survival (CPC 1 or 2) occurred in 23% of patients. The logistic regression model had an accuracy of 79.6%, AUC-PR 0.542, and AUC-ROC of 0.774. The Boosted Trees model had an accuracy of 79.2%, AUC-PR 0.555, and AUC-ROC of 0.774. The Decision Tree Model had an accuracy of 79.3%, AUC-PR 0.490, and AUC-ROC of 0.717. Conclusion: Boosted Trees and Decision Tree ML models performed comparably to the logistic regression model in predicting favorable versus unfavorable neurological outcomes following successful resuscitation from OHCA in advanced-age adults. Given their similar performance, logistic regression may be preferred for its simplicity and interpretability over alternative ML models. Future efforts to improve and ultimately externally validate the model are warranted.
Abstract 4146302: NETosis Attenuating Nanoprobe Improves Survival after Cardiac Arrest
Authors: Howard Chen, Asma Boukhalfa, Kei Hayashida, Yusuke Miyazaki, Rahul Pal, Hushan Yuan, Anand Kumar, Fumito Ichinose, David Sosnovik
Journal: Circulation (2024)

NETosis, the process of neutrophil cell death due to the formation and release of neutrophil extracellular traps (NETs) has been implicated in the pathogenesis of heart disease. NETs are composed of immunogenic DNA fragments and citrullinated histones. The role of NETosis in the context of cardiac arrest and resuscitation (CA/R) is however unknown. We previously reported the development of a Dextran-Thiazole Orange (DTO) nanoprobe, with nanomolar affinity for nucleic acids, that exerts acute anti-inflammatory effects and reduces ischemia-reperfusion injury in mice. We aimed here to determine whether the DTO nanoprobe would also bind to the nucleic acid in NETS, whether DTO could attenuate the intensity of NETosis, and whether this would improve outcomes and survival after cardiac arrest. C57Bl6 mice were arrested for 8 minutes before resuscitation. DTO or unmodified dextran (vehicle control) was injected at the time of resuscitation, and again 4 hours later (n=38 mice). Survival and neurological function were scored daily. Time-domain resolved (lifetime) and conventional fluorescence imaging was performed at 4 hours after resuscitation in 6 additional mice injected with DTO. NETosis was evaluated by protein blot in the hearts of cardiac arrest mice injected with DTO or control. DTO significantly (p&lt;0.05) improved 10-day survival (Fig. A), mean survival (from 4 to 7 days, Fig. B), and neurological function (Fig. C) following CA/R. Lifetime imaging (Fig. D), but not conventional fluorescence imaging (Fig. E) revealed the presence of DTO in the injured heart, liver and kidneys. In the heart, DTO signal was significantly increased in CA/R compared to sham mice injected with DTO or CA/R mice injected with control dextran (Fig. F). Citrullinated H3 and HMGB-1 (High mobility group box 1, a chromatin protein) were both upregulated in CA/R, and were significantly attenuated by DTO injection (Fig. G-I). We show for the first time that NETosis plays a key role in cardiac arrest and resuscitation. DTO is capable of detecting NETosis as well as attenuating it, likely via a reduction in HMGB-1 activity. The modulation of NETosis may provide a new avenue to improve survival after cardiac arrest.
Abstract 4139187: Electrophysiological and Mechanical Characterization of Human Ventricular Myocardium from Patients with Primary or Secondary Cardiac Hypertrophy
Authors: Lorenzo Santini, Jose Manuel Pioner, Cecilia Ferrantini, Chiara Palandri, Lucrezia Giammarino, Monica Musumeci, Chiara Tesi, Elisabetta Cerbai, Corrado Poggesi, Raffaele Coppini
Journal: Circulation (2024)

Left-ventricular hypertrophy (LVH) is an adaptive condition to hemodynamic stress often involving the left ventricle (LV). This pathological condition is associated with clinical complications such as ventricular arrhythmias and diastolic dysfunction, the molecular and cellular mechanisms of which have been poorly investigated in the human heart. We collected myocardial samples from the upper interventricular septum of 132 patients with hypertrophic cardiomyopathy (HCM), 42 patients with aortic stenosis and severe LVH (AoS-LVH) and 12 non-failing non-hypertrophic patients with valve disease (NF-NH), who underwent myectomy operations at our cardiac surgery center. Samples were used to isolate single viable cardiomyocytes from the left ventricle to perform patch-clamp electrophysiological studies and intracellular calcium measurements with fluorescent dyes. Intact trabeculae were also dissected to perform isometric force measurements of electrically-stimulated twitches. Single-cell patch-clamp studies revealed a marked prolongation of action potential duration (APD) in HCM (N=82, mean APD at 90% repolarization=763±252ms at 0.5Hz) and AoS-LVH (N=22, APD90%=579±147ms) samples with respect to NF-NH (N=12, APD90%=447±88ms). In both HCM and AoS-LVH cardiomyocytes, APD prolongation was associated with increased late-Na + current with respect to NF-NH, while L-type Ca 2+ current was enlarged only in HCM samples. Ca 2+ -fluorescence studies revealed markedly slower Ca-transient (CaT) kinetics in myocardial samples from HCM (N=38, mean CaT 50% decay time at 0.5 Hz = 658±179ms) and AoS-LVH patients (N=9, CaT50%= 568±187ms), when compared with NF-NH samples (N=8, CaT50%=283±59ms), paralleled by elevated diastolic [Ca 2+ ]. Twitch force measurements in intact trabeculae revealed prolonged isometric contractions in HCM (N=78, overall twitch duration at 0.5Hz= 730±147ms) and in AoS-LVH patient-samples (N=24, TwD=669±116ms), as compared with NF-NH (N=7, TwD=511±73ms). Force-frequency relationship was flat in pathological samples, while NF-NH trabeculae showed a clear increase in twitch amplitude while increasing pacing rate to 2Hz. Our results suggest that the main features of functional cardiomyocyte remodeling (that is, changes in the expression and/or function of ion-channel and EC-coupling proteins) are qualitatively similar in primary vs. secondary LVH, albeit abnormalities are quantitatively more extensive in HCM samples.
Abstract 4140181: Mechanisms of SGLT-2 Inhibitor Empagliflozin in Attenuating Intramitochondrial Stress and Restoring Mitochondrial Function in Hyperglycemic Cardiomyocyte
Authors: Chen-Hsuan Lin, Yi-hsiung Lin, I-Hsin Liu, Tsung-Hsien Lin, Shih-jie Jhuo
Journal: Circulation (2024)

Systemic hyperglycemia causes tissue damage and triggers cardiovascular disease (CVD). Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are a novel class of glucose-lowering agents that have shown unexpected benefits in clinical trials for the treatment of CVDs. We aim to investigate the underlying mechanisms of how SGLT-2 inhibitors alleviate CVDs associated with elevated glucose stress. iPSC-derived cardiomyocytes (iPSC-CM) were incubated with high glucose concentrations for 72 hours. Mitochondrial function in these cardiomyocytes was assessed by flow cytometry with JC-1 staining and ATP luminescence assay. Intracellular reactive oxygen species (ROS) and intramitochondrial calcium stress were measured using CellROX, MitoSOX, and Rhod-2 AM staining. Patch clamp was employed to determine ion current changes in the cardiomyocytes. Mitochondrial oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were determined using the Seahorse XFe96 analyzer. In addition, qPCR, Western blot, and DM mouse heart histological analysis were performed to assess the regulation of associated molecules. The results indicated that exposure to a high glucose environment caused cardiomyocyte injury and impaired mitochondrial biosynthesis. Empagliflozin exhibited a beneficial effect on mitochondrial function by reducing ROS production and calcium deposition. It also mitigated the reduction in respiratory OCR of cardiomyocytes induced by high glucose incubation. Furthermore, molecular analysis revealed that Empagliflozin attenuated the dysregulation of mitochondrial calcium channels and biosynthesis by reducing associated gene expression, including Bcl2 , Mfn1 , Mx2 , Oas1 , Ant3 , Mcu , Micu1 , Vdac1 , Ryr2 , and Cypd-ppid . Histological analysis of DM mouse hearts demonstrated that reduced MFN2 and ZBP1 were target molecules for hyperglycemia-induced reduction of calcium channel currents in cardiomyocytes and could be restored by Empagliflozin treatment. This study concludes that high glucose stress diminishes mitochondrial calcium channel regulators MFN2 and ZBP1 in cardiomyocyte, which reduces calcium channel currents and leads to sensitization of cardiomyocyte to arrhythmogenesis, resulting in VT/VF. It provides experimental evidence for the clinical efficacy of Empagliflozin in ameliorating CVDs and managing diabetes-related CVDs.