tbuckley/cabot-search huggingface dataset:
Abstract 4141640: The Perinexal Nanodomain Within Intercalated Discs Between Isolated Cardiomyocyte Pairs Modulates Sodium Currents
Authors: Xiaobo Wu, Sharon Swanger, Steven Poelzing, Robert Gourdie
Journal: Circulation (2024)

Background: Ephaptic coupling (EpC), a form of intercellular communication between excitable cells, has been proposed to occur at the perinexus, a sodium channel-rich nanodomain within the intercalated disc (ID). Previous studies suggest that widening the perinexus can influence EpC by altering sodium ion availability, which in turn determines perinexal sodium currents (INa). However, there is a lack of direct evidence for a causal relationship between the perinexus and ephaptic coupling. This study aims to develop a novel approach to directly measure the effect of perinexal expansion on INa. We hypothesize that widening the perinexus increases INa in cardiomyocytes that maintain intact IDs. Methods: We selected pairs of mouse cardiomyocytes connected through IDs, preserving intact perinexi. Initially, the feasibility of measuring the whole-cell INa from the entire cell pair was investigated using single patch clamp. If feasible, widening the perinexus should increase the whole-cell INa by enhancing perinexal INa. Isolated single cardiomyocytes and cardiomyocyte pairs from ventricles were used for whole-cell INa recordings. A de-adhesion peptide named βadp1, previously demonstrated to widen the perinexus, was used. Results: We found that the whole-cell INa in cell pairs can be stably measured, showing no differences in INa density compared to single cells (panels A&amp;B in Figure). Notably, the duration of the INa tracing in cell pairs is short relative to single cells primarily due to shorter inactivation phase in cell pairs (panel C), suggesting a lack of available sodium ions in the ID caused by sodium channel activation. It was also confirmed that βadp1 does not affect INa in single cells, consistent with previous reports. Importantly, we demonstrated that βadp1 significantly increased INa (panel D), likely due to faster sodium influx during sodium channel activation phase. Conclusions: The cell pair model is a feasible method for measuring whole-cell INa with single patch clamp, and widening the perinexus increases INa in this model, which supports the hypothesis that EpC is occurring between the cells. Our findings may offer a new approach to study the impact of structural changes in IDs on ionic currents.
Abstract 4140872: Causes of 30-Day Readmissions Following Permanent Pacemaker Implantation in Dialysis-Dependent End-Stage Renal Disease Patients: Analysis of the National Readmission Database 2020
Authors: Vivek Jha, Taha Teaima, Rohan Gajjar, Badri Aryal, Andres Quevedo Ramirez, Sadichhya Karki, Supriya Jha
Journal: Circulation (2024)

Background: Permanent Pacemaker (PPM) implantation is recognized as a class I indication treatment for patients with high-grade Atrioventricular (AV) blocks, infra-Hisian conduction blocks, and symptomatic sinus node diseases such as sinus bradycardia. There remains a scarcity of data regarding the impact of dialysis-dependent End-Stage Renal Disease (ESRD) on PPM implantation outcomes, particularly in terms of readmission rates. We aim to evaluate short-term readmissions in dialysis-dependent ESRD patients post-PPM placement, utilizing data from the National Readmission Database (NRD). Methods: The NRD for the year 2020 was used to identify dialysis-dependent ESRD adults who underwent PPM implantation, employing ICD-10 CM and PCS codes. We focused on outcomes including 30-day readmission rates, length of stay (LOS), total hospital charge (THC), and predictors of readmissions. Both multivariate and univariate logistic and linear regression analyses were employed to assess outcomes and adjust for potential confounders. Results: Out of 2,497 dialysis-dependent ESRD patients who underwent PPM implantation, 2,353 were discharged alive. Within 30 days of discharge, 540 (22.9%) patients were readmitted. Those readmitted had a longer LOS and higher comorbidity burden but were similar in age, sex, hospital characteristics, and household income status compared to those not readmitted. Readmissions incurred an additional average THC of $103,599 and an average LOS of 7.3 days. The top five causes of readmissions were hypertensive heart disease with heart failure (11.3%), sepsis (9.9%), fluid overload (2.4%), hypoglycemia without coma in type II diabetes mellitus (2.0%), and non-rheumatic aortic valve stenosis (1.7%). Conclusion: This analysis reveals that 22.9% of dialysis-dependent ESRD patients who underwent PPM implantation were readmitted within 30 days, resulting in extended LOS and increased THC. These readmissions negatively impact patient outcomes and exacerbate the burden on healthcare resources. Optimizing the management plans for this patient group is crucial to enhancing outcomes and using healthcare resources more effectively.
Abstract 4141626: A closed-loop system based on piezoelectric thin-film sensors and photothermal nanomaterials enables precise renal denervation for the treatment of hypertension
Authors: Chengzhe Liu, Liping Zhou, Lilei Yu
Journal: Circulation (2024)

Background: Since renal sympathetic nerves play a crucial role in the pathogenesis of hypertension, renal denervation (RDN) has emerged as a new solution for hypertensive patients, especially those with refractory hypertension. However, clinical trials have shown inconsistent results with current RDN techniques. This may be attributed to the short duration of effects induced by nerve fiber regeneration after ablation and the lack of measures to localize and assess efficacy. Hypothesis: In this study, we attempted to construct a sustainable closed-loop RDN system and overcome these limitations. Methods: We designed a new closed-loop RDN system containing a monitoring module with piezoelectric thin-film sensor (PTFS) and an intervention module with Pd nanopartical shell (PdNPS)-mediated photothermal nerve ablation. The feasibility and safety of this closed-loop system was explored in canine models of acute and chronic renal sympathetic nerve stimulation simulating hypertension, respectively. Results: In vivo experiments showed that PTFS on the surface of the renal artery enabled monitoring and collection of arterial pulsations and blood pressure. The self-monitoring function based on PTFS can guide PdNPS to maximize RDN. During the treatment window of 90-120s, PdNPS could maintain an ablation temperature of 58-62°C under NIR irradiation to inhibit renal sympathetic nerve activity and function. In the hypertension simulation model, the increase in blood pressure was 54.65% lower in the PdNPS group compared to the control group (p&lt;0.05). Histologic testing showed that PdNPS ablation resulted in necrosis and degeneration of the renal sympathetic nerves, whereas the renal arteries were structurally intact and functioned normally. In addition, the increase in blood pressure after 1 month was 52.84% lower in the PdNPS group compared with the sham group (p&lt;0.05), suggesting microinjection of PdNPS photothermal ablation is sustainably effective. Conclusion: This novel closed-loop system has the potential for safe and effective RDN, which would provide a new therapeutic strategy for refractory hypertension and even chronic diseases of the autonomic nervous system.
Abstract 4141277: Continuous nitric oxide inhalation in a murine model of bronchopulmonary dysplasia and pulmonary hypertension
Authors: Luca Zazzeron, Eizo Marutani, Paul Lichtenegger, Fumito Ichinose
Journal: Circulation (2024)

Introduction: Abnormal lung development is associated with respiratory disease and pulmonary hypertension (PH) in children. PH associated with bronchopulmonary dysplasia (BPD) carries significantly morbidity and mortality due to right ventricular (RV) failure. Aim: to develop an animal model of BPD and PH and examine the effects of chronic nitric oxide (NO) inhalation. Methods: We exposed C57bl/6J mouse pups to 11% FiO 2 starting on post-natal day 2-4 with (11%-NO) or without (11%) continuous inhalation of 10 ppm NO for 8 weeks. Control mice breathed air (21%). At age 8 weeks we evaluated the degree of lung injury by measuring arterial PO 2 while breathing 11% FiO 2 , by obtaining lung pressure-volume curves and by pathological evaluation; on transthoracic echocardiography we evaluated the degree of PH by assessing the ratio between the pulmonary artery acceleration time and the ejection time (PAAT/ET), and the RV function by assessing the tricuspid annular plane systolic excursion (TAPSE). We measured RV systolic pressure (RVSP) and RV hypertrophy with the Fulton’s ratio. Results: 11% and 11%-NO mice compared to controls had lower PaO 2 (42.5±5.1 vs. 42.3±5.4 vs. 51.8±1.4 mmHg, p&lt;0.01), increased lung compliance (51.3±9.6 vs. 46.9±3.2 vs. 35.0±3.3 mL/cmH 2 O, p&lt;0.001), reduced alveolarization, severe small vessel muscularization and vascular rarefaction (Fig. 1 and 2). Treatment with NO ameliorated the reduction in PAAT/ET and TAPSE that was observed in 11% mice compared to controls (11%-NO vs. 11% vs. 21%: PAAT/ET 0.27±0.03 vs. 0.22±0.04 vs. 0.32±0.04, p&lt;0.0001, TAPSE: (0.85±0.16vs. 0.67±0.10 vs.1.1±0.2 mm, p&lt;0.0001). Similarly, the RVSP of 11% mice was significantly elevated compared to control mice and diminished by NO treatment (11% vs. 21% vs. 11%-NO: 84±7 vs. 28±4 vs. 66±7 mmHg p&lt;0.0001). RV hypertrophy in 11% mice was more severe than in 11%-NO mice compared to controls (Fulton’s ratio: 52±8% vs. 42±6% vs. 22±2%, p&lt;0.0001). The median RV cardiomyocytes cross-sectional area significantly increased in both 11% and 11%-NO mice compared to controls but at a lesser extent in the 11%-NO mice (198[194-201 vs.181[178-183] vs.149[87-240] mm 2 , p&lt;0.0001) (Fig. 3). Conclusions: we developed a new mouse model of BPD with associated severe PH and RV dysfunction. Continuous inhaled NO did not improve neonatal hypoxia-induced lung injury but ameliorated PH, RV hypertrophy and function. Translation of this therapy to children with BPD and PH may improve clinical outcomes.
Abstract 4141043: Upregulation of Dynamin 2 (DNM2) Increases Mitochondrial Fission and Cell Proliferation in Pulmonary Arterial Hypertension
Authors: Asish Das Gupta, Kuang-Hueih Chen, Danchen Wu, Patricia Lima, Ashley Martin, Jeffrey Mewburn, Ruaa Al-Qazazi, Isaac Emon, Pierce Colpman, Siddartha Yerramilli, Oliver Jones, Charles Hindmarch, Francois Potus, Sebastien Bonnet, Stephen Archer
Journal: Circulation (2024)

Introduction: Mitochondrial fission is mediated by dynamin related protein-1 (Drp1) activation; however, to complete fission, we have evidence that Drp1 requires assistance from the GTPase dynamin 2 (DNM2). Hypothesis: DNM2 interacts with Drp1 to regulate mitotic fission and cell cycle progression, permitting the hyperproliferative phenotype of pulmonary artery smooth muscle cells (PASMC) in pulmonary arterial hypertension (PAH). Methods: Colocalization of Drp1 and DNM2 was assessed using STED super resolution confocal microscopy. Interaction of Drp1 and DNM2 was confirmed by immunoprecipitation. The role of DNM2’s GTPase domain in mitochondrial targeting was assessed by heterologous expression of truncated constructs. Changes in transcriptomic signature from silencing DNM2 in PAH human PASMC (hPASMC) were measured by RNA-seq. DNM2 expression in control vs PAH was quantified in hPASMC (n=4-5/group) and lungs from human (n=5/group), monocrotaline (MCT) (n=4-5/group) and SU5416/hypoxia (Su/Hx) (n=4-5/group) induced rodents using immunoblots, immunohistochemistry and immunofluorescence. DNM2’s effects on cell proliferation, cell cycle and apoptosis were assessed by flow cytometry. siDNM2 was nebulized to rats with established MCT-PAH. Results: DNM2 is significantly increased in human and rodent PAH and silencing DNM2 reduces mitochondrial fission and cell proliferation and induces apoptosis and cell cycle blockade in the G0/G1 phase in PAH PASMC. DNM2 and Drp1 interact at mitochondrial fission sites. DNM2’s translocation to the mitochondria is Drp-dependent and requires DNM2’s GTPase domain. Silencing DNM2 downregulates the Regulator of Cell Cycle, RGCC . Augmenting DNM2 in normal PASMC induces mitochondrial fission and cell proliferation. miR-124-3p, which negatively regulates DNM2, is decreased in PAH PASMC. Augmenting miR-124-3p decreases DNM2 expression, inhibits fission and proliferation and induces apoptosis in PAH PASMC. Silencing STAT3 (also negatively regulated by miR-124-3p) reduces DNM2 and inhibits fission. siDNM2 regresses PAH in MCT-PAH rats. Conclusion: DNM2 binds to Drp1 and translocates to mitochondria, regulating fission. A pathological increase in DNM2 expression, driven by decreased miR-124a-3p and STAT3 activation, increases mitochondrial fission, proliferation and inhibits apoptosis in PAH PASMC. DNM2 regulates cell proliferation via RGCC. DNM2 is a fission mediator and its regulatory pathway offers potential PAH therapeutic targets.
Abstract 4141659: Uncovering Sex Bias in Machine Learning Algorithms for Detecting Acute Myocardial Infarction using Electrocardiographic Data
Authors: Yasoda Sai Ram Kandikonda, Abhinav Goyal, Jessica Zegre-Hemsey, Lekshmi Kumar, David Wright, Marly Van Assen, Judy Wawira, Sukardi Suba, Mary Carey, delgersuren bold, Cheng Ding, Alex Fedorov, Jiaying Lu, Runze Yan, Xiao Hu, Ran Xiao
Journal: Circulation (2024)

Introduction: Acute myocardial infarction (AMI) is a life-threatening manifestation of cardiovascular disease so timely detection and intervention are crucial for improving patient outcomes. Increasingly, machine learning (ML) algorithms are being leveraged to analyze 12-lead electrocardiograms (ECGs) to optimize early and accurate triage for AMI. However, the potential inherent sex bias within these data-driven algorithms remains insufficiently explored. This study aims to uncover potential sex bias in ML algorithms through a systematic and well-controlled investigation. Methods: Utilizing a public ECG dataset (PTBXL) with cardiologist annotations of AMI and non-AMI classes, we conducted sex-based resampling to obtain datasets with varying male-to-female sample ratio from 0.5 to 1.5, keeping the AMI to non-AMI ratio constant at 1:2 for each sex group. We evaluated the performance of ML models derived from these datasets on ECGs from male and female subgroups. The process was repeated 30 times with random subsampling. The area under the precision-recall curve (AUCPR) was used as the performance metric because it is robust to class imbalance issues. Results: The models consistently performed better on the male subgroup, even as the number of female samples increased. At a male-to-female ratio of 0.5 (male: 2394; female: 4788), the mean AUCPR for males was 0.626 ± 0.03, compared to 0.573 ± 0.02 for females. This trend persisted at a balanced ratio of 1.0 (4788 samples each), with an AUCPR of 0.651 ± 0.02 for males and 0.592 ± 0.02 for females. At a ratio of 1.5 (male: 7182; female: 4788), the AUCPR for males was 0.667 ± 0.02, versus 0.598 ± 0.02 for females. All comparisons were statistically significant (p &lt; 0.05, two-sample Student t-tests). Discussion: Despite an increased number of female samples, the consistently better performance of the model to detect AMI in males suggests a potential bias in the model. We hypothesize that this bias may be related to inherent differences in the distribution of ECG patterns between male and female subgroups. Our findings indicate that simply balancing the dataset by increasing the female sample size is insufficient to mitigate bias. Addressing disparities in healthcare data requires more nuanced strategies beyond data balancing. Future work should explore alternative approaches to overcome sex bias in the application of ML algorithms in the interpretation of ECGs in patients with suspected AMI.
Abstract 4140984: Palliative Care Interventions Effect on Quality of Life and Symptoms in Patients with Heart Failure: An Updated Systemic Review and Meta-analysis
Authors: Omar Almaadawy, Manar Mabrouk, Mohamed Elnady, Rahma AbdElfattah Ibrahim, Abdul Rhman Hassan, Ahmed Eldaidamouni, Salma Allam, Amr Elzahaby, Moaz Darwish, Aya Alrawi, Mustafa Ahmed
Journal: Circulation (2024)

Introduction: Heart failure (HF) is a prevalent medical condition, affecting approximately 6.7 million Americans. Patients with HF frequently experience comorbidities such as depression and anxiety, which can lead to diminished quality of life. According to the World Health Organization (WHO), palliative care may be beneficial for these patients in addressing their complex physical, mental, and social needs. Therefore, an assessment of palliative care involvement in HF patients is warranted to determine its impact on improving quality of life, alleviating symptoms such as dyspnea, depression, and anxiety. Hypothesis: The aim is to assess the impact of palliative care interventions on the quality of life, dyspnea, anxiety, and depression in patients with HF. Methods: A systematic review and meta-analysis were conducted on clinical trials retrieved from Scopus, Cochrane, PubMed, Embase, and Web of Science databases from their inception until March 2024. Studies reporting on the impact of palliative care interventions on the quality of life of patients with HF were included. The primary outcome was the effect on quality of life, while the effects on dyspnea, depression, and anxiety were secondary outcomes. Data from the studies were pooled using RevMan V5.4, and changes in the mean difference from baseline and confidence intervals (CI) were calculated for each outcome. Results: The meta-analysis included eleven studies, predominantly randomized controlled trials, with a total of 1662 participants, 812 of whom received palliative care interventions. The analysis revealed a significant improvement in the mean change from baseline within the intervention group compared to usual care. Specifically, the quality of life showed a mean difference change from the baseline of 1.35 (95% CI: 0.88 to 1.82), anxiety improved with a mean difference change from baseline of 0.30 (95% CI: 0.03 to 0.58), and dyspnea showed a mean difference change from baseline of 1.0 (95% CI: 0.74 to 1.26). However, there was no significant difference in the mean change from baseline for depression between both groups. Conclusion: Palliative care interventions are associated with significant improvements in quality of life, anxiety, and dyspnea in patients with heart failure compared to usual care. However, there is no significant impact on depression. These findings support the integration of palliative care into the management of heart failure patients to enhance their overall well-being.
Abstract 4140868: Perceptions about Diversity, Equity, and Inclusion among Cardiovascular Fellows-in-Training
Authors: Estherland Duqueney, Ersilia DeFilippis, Amit Goyal, Gurleen Kaur, Howard Julien, Lauren Eberly
Journal: Circulation (2024)

Background: Efforts to promote diversity, equity, and inclusion (DEI) within cardiology have been proposed and implemented to varying degrees. However, the perceptions of cardiovascular (CV) fellows-in-training (FIT) have not been characterized. Therefore, we sought to gauge the experiences of CV FIT at their institutions and the extent to which DEI is valued and embraced as a core mission. Methods: We conducted a nationwide survey of CV FIT from May to June 2021, utilizing the CardioNerds platform to recruit participants. The 25-question survey assessed FIT perceptions of diversity, institutional prioritization of DEI efforts, and the commitment to anti-racism as part of the fellowship curriculum on a Likert scale from 1 to 5, supplemented by open-ended questions with free-text responses. The authors reviewed narrative comments to identify common themes. Results: A total of 101 fellows-in-training (39.2% female, 37.6% as Asian, 13% as Black, 9% as Hispanic/Latinx; and 36% as international medical graduates) responded to our survey. The majority (67%) of respondents believed that health equity was valued by their program, and most (65%) considered diversity and health equity as priorities of their programs. While 58% of all respondents felt there were physicians in leadership positions who looked like them, 92% of Black FIT disagreed. Respondents highlighted strengths of their institutions including a diverse existing workforce and institutional commitment to DEI. However, suggestions for improvement focused on formal equity training, community outreach opportunities, and recruitment of underrepresented in medicine faculty in leadership positions. Conclusion: CV FIT recognize that DEI is valued by their institutions and training programs, but persistent challenges remain. Black CV FIT did not feel adequately represented in leadership, highlighting a need for more Black representation in faculty leadership. FIT desire formal cardiovascular equity training and community outreach opportunities, indicating a need for standardized health equity and antiracist curricula in cardiology programs.
Abstract 4141523: Human-Centered Design to Tailor Telehealth Cardiac Rehabilitation to Diverse Populations: The MCNAIR Study
Authors: Rae Denise Oanesa, Namratha Atluri, Yehia Z Ali, Shireen Khoury, Vanessa Lageza, Patricia McNair, Greg Merritt, Sonali Mishra, Daniel Forman, Erin Spaulding, LaPrincess Brewer, Jessica Golbus, Seth Martin, Brahmajee Nallamothu, Alexis Beatty
Journal: Circulation (2024)

Background: Delivering cardiac rehabilitation (CR) by telehealth may increase participation and promote equitable access to CR. Our objective was to tailor a patient-centered telehealth CR program to diverse populations. Methods: We recruited participants with varying CR experience (e.g. attended &gt;1 session, did not attend CR, and caregivers) between January and September 2023 from four US academic medical centers. Participants engaged in human-centered design sessions on CR perspectives and a proposed telehealth CR program. Sessions were qualitatively analyzed using rapid template analysis with pre-selected behavioral science constructs and other emergent codes. Based on participant feedback, we iteratively revised the telehealth CR program and created an implementation toolkit. Results: Among 21 participants (76% ≥65 years, 50% female, 60% non-Hispanic White; 90% attended &gt;1 session, 10% caregiver of a CR participant, 5% prefer not to answer), CR was overall regarded as valuable. Benefits included accountability, confidence, and feeling better. Social support was appreciated from family, friends, program co-participants, and CR staff. Participants emphasized the importance of early goal setting, accountability, and program individualization. Participants thought that using technology for telehealth CR could be helpful for accountability, facilitating relationships, and convenience. However, some participants had concerns about safety, especially at the start of their telehealth program, and desired checks such as a monitoring device or observation of exercise over video. Through human-centered design, safety protocols and technology training were developed, which participants thought addressed their concerns about participating in telehealth CR. The implementation toolkit informed by human-centered design included a participant journey, safety plan, home exercise plan for use during and after CR, and scripts for technology training and telehealth visits. Selected quotes are presented in Figure 1. Conclusions: We developed a patient-centered telehealth CR program and implementation toolkit. Future research will test the comparative effectiveness of in-person and telehealth CR on patient-centered outcomes.