tbuckley/cabot-search huggingface dataset:
Abstract 4148046: A Comparison of Anxiety and Depression in Patients with Symptoms of Palpitations Compared to High Risk Arrythmia Patients.
Authors: Mark Treuth, Kunnal Patel, Justin Rissmiller, Veera Holdai
Journal: Circulation (2024)

Background: Palpitations are the second most common presenting symptom for cardiology visits. The prevalence of anxiety and depressive disorders in patients with symptoms of arrhythmia, palpitations, is well documented but how this compares to patients at the greatest risk for major cardiac arrythmia is unknown. Objectives: The purpose of this study was to determine the prevalence of anxiety or depression in patients with symptomatic palpitations vs patients at risk for major cardiac arrhythmia (congestive heart failure) and further evaluate the effects on their quality of life using the SF-36 assessment tool. Methods: Patients with palpitations (50 subjects) or prior ICD (50 subjects) were given the General Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire (PHQ-9) and the Short Form Health Survey (SF-36). Results: There was an insignificant trend for increased anxiety, with a mean GAD-7 score in palpitations group of 4.14 vs 3.04 in CHF group with anxiety prevalence in 40% palpitations and 28% of ICD patients. The mean score of PHQ-9 in palpitations group is 4.84 vs 4.96 in CHF group with 38% of the palpitation group having depression compared to 44% of the ICD group. The SF-36 physical function domain showed that the palpitations group was more functional than the ICD group with a mean score of 0.709 in palpitations group vs 0.513 in CHF group (P &lt;0.05.) Subjective frequency of palpitations had a mean of 3.47 in the palpitation group vs 1.5 in the CHF group with P&lt;0.05. Conclusions: Patients presenting with symptomatic palpitations have more symptoms of anxiety than patients at risk for major arrythmia, but have less functional limitations than the ICD group, as expected. There is a non-significant trend to more anxiety in the palpitations group, but both groups are far above populations norms of 2-4%. Depression is not different between the groups but both groups are far above the population averages of 5-6%. Patients with palpitations have fewer physical limitations but have at least an equal amount of anxiety and depression as a far more ill group of patients. It is a standard of care to treat symptomatic palpitations due to PVCs with beta blockers; this will not help symptoms of anxiety and it may worsen depression. When seeing patients presenting with palpitations, or patients with chronic heart disease and an ICD, we should consider an evaluation for anxiety and depression.
Abstract 4147887: <i>Cardiopulmonary Best Abstract Award:</i> Mitochondrial Dysfunction in Right Ventricular Cardiomyocytes Drives Ceramide-Mediated Lipotoxicity in Pulmonary Arterial Hypertension
Authors: Maki Niihori, Joel James, Odunayo Lawal, Ruslan Rafikov, Olga Rafikova
Journal: Circulation (2024)

Introduction: Pulmonary arterial hypertension (PAH) is a progressive and fatal disease with unmet medical needs. Patient outcomes primarily depend on the ability of the right ventricle (RV) to maintain adequate function, yet no therapy preventing RV dysfunction is currently available. Previous studies have demonstrated that patients with PAH exhibit an impaired fatty acid (FA) metabolism and RV steatosis. Furthermore, this RV lipotoxicity was associated with a substantial accumulation of the cardiotoxic sphingolipid ceramide. In this study, we utilized a novel rat model of severe mitochondrial dysfunction (MD) induced by humanized G206C mutation in the NFU1 protein to investigate the role of MD in the RV FA metabolism. Hypothesis: We hypothesized that MD severely impairs FA metabolism, leading to the upregulated synthesis of cardiotoxic ceramides. Methods: The RV functional analysis and mitochondrial respiration were assessed in the NFU1 G206C rats with a developed PAH phenotype and age-matched wild types (WTs). The FFA transporter expression level and cardiac lipotoxicity markers were compared in the isolated RV and left ventricle (LV) cardiomyocytes (CMs). To address the role of ceramides, we investigated the protective capacity of the inhibitor of dihydroceramide desaturase-1 (DES1), catalyzing the final step in the de novo ceramide synthesis. Results: RV but not LV CMs showed impaired mitochondrial respiration in NFU1 G206C rats. Consistent with findings in PAH patients, these changes were associated with a significant RV steatosis and an increase in the expression of free FA transporter, CD36, and DES1, both observed explicitly in NFU1 G206C RV CMs. Treatment with a DES1 inhibitor (DES1i, 2.5 mg/kg i.p., every other day for 4 weeks) attenuated the PAH phenotype in NFU1 G206C rats (RV systolic pressure: WTs vs. NFU1 G206C vs. NFU1 G206C +DES1i; 23.8 ± 1.3 vs. 32.7 ± 3.7 vs. 27.1 ± 1.3 mmHg, p &lt; 0.001 (ANOVA), N=5:), by inhibiting RV hypertrophy (Fulton Index: 0.27 ± 0.01 vs. 0.30 ± 0.01 vs. 0.27 ± 0.01, p &lt; 0.05 (ANOVA), N=5) and improving mitochondrial function in CMs. Conclusion: MD is a significant contributor to RV dysfunction, lipotoxicity, and enhanced ceramide synthesis. The protective effect of DES1 inhibition underscores the therapeutic potential of targeting ceramide pathways in PAH.
Abstract 4147910: 22q11 Deletion Syndrome: A Potenitial Risk Factor For Left Pulmonary Artery Hypoplasia and Need For Intervention in Patients With Congeital Heart Disease
Authors: Shannon Oliver, Cameron Ward
Journal: Circulation (2024)

Background: Individuals with 22q11 deletion syndrome have a mutation in the TBX1 gene which is associated with the formation of cardiac outflow tracts. Animal studies have shown that mice with TBX1 gene mutations have smaller left pulmonary arteries compared to wild type mice, defined by a reduced left pulmonary artery (LPA) to right pulmonary artery (RPA) ratio. A single study has shown this translates to humans with 22q11 and structurally normal hearts. We sought to determine if this is also true for patients with congenital heart disease and whether this finding has clinically significant links with reference to the need for increased intervention upon the LPA. Method: We performed a retrospective analysis of patients at our centre who underwent surgical repair of Tetralogy of Fallot, Truncus Arteriosus or Interrupted Aortic Arch between 2007 and 2022, with follow up to 2023. 134 patients were identified and were divided into two groups, those with 22q11 deletion syndrome (19 patients) and the control group (115 patients). The LPA to RPA ratio on initial and most recent echocardiogram, intervention on the LPA at initial surgery and subsequent reintervention on the LPA were compared between the two groups. Results: The 22q11 deletion and control group had a similar mean age at time of study 6.9±3.4 versus 5.9±3.8 years. Tetralogy of Fallot was overrepresented in the control group compared to the 22q11 deletion group (87.8% versus 42.1%). Patients with 22q11 deletion had a reduced LPA to RPA ratio compared to the control group on both the initial (0.84±0.17 versus 1.03±0.18; p&lt;0.001) and most recent (0.76±0.17 versus 1.03±0.27, p=0.002) echocardiogram. Patients with 22q11 were more likely to have intervention on the LPA in their initial surgery compared to the control group (36% versus 8.7%, p = 0.003). There was no statistical differences between rates of LPA reintervention between the 22q11 deletion group and the control group (26% versus 10.7%; p=0.070). Conclusion: Patients with 22q11 deletion syndrome are more likely to have reduced LPA to RPA ratio and need intervention on the LPA at the initial surgery, despite Tetralogy of Fallot (the only of the three lesions known to be associated with LPA stenosis) being over represented in the control group. The most recent echocardiogram showed a reduced LPA to RPA ratio in the 22q11 group, so we suspect that whilst we demonstrated no difference in rates of reintervention, this could change with longer follow up.
Abstract 4147980: Barriers and Facilitators to Clinician Engagement in an Implementation Science-Informed Digital Health Intervention for Depression Treatment in Patients with Coronary Heart Disease
Authors: Kain Kim, Nohora Ospina, Meredith Diamond, Samantha Flores, Jennifer Mizhquiri Barbecho, Nathalie Moise
Journal: Circulation (2024)

Introduction: Nearly 1 in 5 coronary heart disease (CHD) patients experience depression, an independent risk factor for major adverse cardiovascular events. Yet, depression remains undertreated in CHD patients, and few existing implementation strategies address gaps in AHA depression treatment guidelines. Although digital health interventions may help provide patient preference-driven treatment and support, provider perceptions of these tools are poorly understood. Methods: From 2019 to 2024, we randomized 12 Columbia University Medical Center affiliated primary care and cardiology clinics to timing of a multi-level intervention, which includes problem-solving meetings for mental health social workers (MHSW), cardiologist/PCP (provider) education, and integration of a psychoeducation, activation, and treatment digital selection tool (“iHeart”). We previously found pre-post improvements in provider referral/prescribing rates (25 vs. 40%). Informed by the Consolidated Framework for Implementation Research 2.0, we conducted 1:1 interviews on treatment barriers and iHeart tool/digital health acceptability with 2-3 providers/MHSW/administrators per clinic in the post-implementation phase. We conducted thematic analyses, incorporating a data-driven inductive approach. Results: To date, 10 clinics completed the post implementation phase, and 20 clinicians consented to interviews. Key themes included 1. dissatisfaction with current depression screening and referral practices 2. Poor integration of digital therapeutics into existing clinic resource hubs, 3. Competing time and priorities and 4. Digital literacy in older, non-English speaking, or low-income patients limits uptake. For specific iHeart feedback, barriers included needing integration into the pre-visit screening workflow and confidentiality concerns. However, providers felt it would streamline the burdensome referral process and improve overall patient communication on mental health issues. For future stages, providers recommended clarifying tool integration infrastructure (e.g. for individual providers or entire clinic), engaging patient family members, and incorporating a navigation team component to orient patients with technological or literacy barriers. Conclusion: A multi-level digital health implementation strategy may help address existing clinician barriers to depression treatment in individuals with CHD. Future studies will examine impact on patient symptoms, management patterns, and treatment uptake.
Abstract Sa904: Relationship between time of occurrence and survival of in-hospital cardiac arrests triggered by medical adverse events(Nationwide medical adverse events database in Japan)
Authors: Yu Kanayama, Takeyuki Kiguchi, Chinatsu Nakai, Yasutaka Hamai, Chika Nishiyama, Masahiko Nitta, Tatsuya Norii, Taku Iwami
Journal: Circulation (2024)

Background: The outcome of in-hospital cardiac arrest (IHCA) has improved over the past decade, although the survival rate is still approximately 25%. Some cases of IHCA are triggered by medical adverse events, and their outcomes might be different by time when how many staffs is available. But the relationship between the time of occurrence and outcome remains unclear. The aim of this study is to compare the survival outcomes of IHCA at night with those during the daytime using the nationwide medical adverse events database in Japan. Methods: We searched the Japan Council for Quality Health Care nationwide in-hospital adverse events database, which registered 1 million cases per year, from 2010 to 2023. We extracted cases of IHCA and analyzed the cases by time of occurrence, grouping them into day time shift (8am-4pm), midnight shift (4pm-0am), and late night shift (0am-8am). The primary outcome was survival to discharge, and we performed multivariate logistic regression to adjust for age, sex, holiday, cause of medical adverse events, event location, occupation of the involved party, occupational history of the involved party and assignment period of the involved party as potential confounders. Result: A total of 4,252 cases were included during the study period. The most common age group was over 70years old (54.2%, n = 2,303 /4,252). 2,627 patients (61.8%) were male. The number of IHCA per time period was 1949 (45.8%) in the day time shift, 1,349 (31.7%) in the midnight shift and 954 (22.4%) in the late night shift. The most common cause of medical adverse events in all time periods was treatment or procedures. However, the rate of medical care was higher in the late night shift. Regarding the location of the event, the general ward was the most common location at all times. Multivariate logistic regression for survival on discharge yielded an adjusted odds ratio of 1.56 (95% confidence interval [CI]: 1.30–1.86) ,1.33 (95% CI: 1.11–1.59) for the day time shift and midnight shift compared to the late night shift. Conclusion: Approximately 20% of in-hospital cardiac arrests due to medical adverse events occurred on the late night shift, with poor outcomes. Time of occurrence was associated with survival to discharge among IHCA cases that were identified in the nation-wide adverse events database.
Abstract Su103: Targeting succinate metabolism for neuroprotection after cardiac arrest and resuscitation
Authors: Jun Hagiwara, Lance Becker, Kanako Ito-Hagiwara, Yusuke Endo, Kei Hayashida
Journal: Circulation (2024)

Background: Succinate dehydrogenase (SDH) is a key enzyme involved in succinate accumulation during ischemia and its subsequent oxidation upon reperfusion, leading to excessive reactive oxygen species production. Malonate, a competitive inhibitor of SDH, has emerged as a promising candidate for selective SDH inhibition to reduce reperfusion injury. However, studies targeting succinate metabolism for neuroprotection after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) are still extremely limited. Methods and Results: Adult male Sprague-Dawley rats were intubated, mechanically ventilated, and instrumented under anesthesia. Microcatheters were inserted into the left femoral artery for monitoring blood pressure and the left femoral vein for drug administration. The animals were subjected to 10 minutes of asphyxial CA, followed by CPR with epinephrine injection and finger chest compressions. The animals were assigned to three groups based on intravenous drug injections: dimethyl malonate injected during CA (DMM-CA group, n = 11), dimethyl malonate injected at the initiation of CPR (DMM-STAT group, n = 8), and saline injected during CA (saline group, n = 11). The animals were extubated 2 hours post-resuscitation, then were returned to their cages with easily accessible food and water and were monitored in a rodent facility with controlled room temperature. At 72 hours after a return of spontaneous circulation (ROSC), the survival rates were 72.7% in the DMM-CA group, 50.0% in the DMM-STAT group, and 36.4% in the saline group. The DMM-CA group exhibited a significantly higher survival rate (Kaplan–Meier analysis, P &lt; 0.05) and better neurological function scores at 72 hours after ROSC (Mann-Whitney U test, P &lt; 0.05) compared to the saline group. There was no statistically significant difference in survival rates between the DMM-STAT and saline groups. To further test the impact of succinate accumulation during CA on survival, dimethyl succinate was intravenously administered during CA in a separate group of animals subjected to 10 minutes of asphyxial CA (n = 6). None of the animals that received dimethyl succinate survived for 48 hours, confirming that succinate accumulation during CA contributes to mortality after CPR. Conclusion: Our results demonstrated that SDH inhibition was beneficial when initiated during CA in rats. Further studies are warranted to elucidate the impact of succinate metabolism on outcomes after CA and CPR.
Abstract 4148007: Cardiovascular outcomes with Glucagon-like Peptide-1 receptor agonists and Sodium-glucose Cotransporter-2 Inhibitors in patients with ischemic stroke in the community
Authors: Mohammad Ali Sheffeh, Andres Estrada Magana, Jose Medina-Inojosa, Laura Ortega Aviles, Rosana Bianchettin, Betsy Medina-Inojosa, James Klaas, Robert Brown, Francisco Lopez-Jimenez
Journal: Circulation (2024)

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) have known cardiovascular benefits. We aimed to assess the efficacy of GLP1-RA or SGLT2i initiation in reducing mortality or cardiovascular events in a community-based cohort of adults with ischemic stroke. Methods: Patients ≥18 years old admitted for acute ischemic stroke between Jan 2000 and June 2022 were identified using the Rochester Epidemiology Project. Subjects were considered exposed to SGLT-2i or GLP1-RA if they were treated with either medication after the index stroke and before the primary (all-cause mortality) or secondary outcomes (MI, recurrent ischemic stroke or composite). Kaplan-Meier curves and Cox models are shown in the Figures . Results: We included 7044 subjects, mean age 72±14 yr, 52% male, 94% white, over a median follow-up of 3 [1-7] years, 416 subjects (6%) had a second stroke, 426 (6%) had an incident MI and 3738 (53%) died. Those on SGLT2i/GLP1-RA had a decreased risk for mortality, incident MI, and composite in the univariate analysis. These associations remained significant after multivariable adjustment and were not affected by minimum time of exposure Figure 1&amp;2 . SGLT2i/GLP1-RA use was associated with recurrent ischemic stroke in the multivariate analysis Figure 2C . All associations remained significant in most sub-analyses of individual medications except for the association between GLP1-RA and recurrent stroke Figure 3 Conclusions: SGLT2i or GLP-1 RA use was associated with decreased mortality and risk of myocardial infarction and recurrent stroke in patients with ischemic stroke.
Abstract Sa607: Automated Analysis of Arterial Waveforms and Diastolic Blood Pressure During Cardiopulmonary Resuscitation in a Swine Cardiac Arrest Model
Authors: Zachary Sharpe, Nicholas Greer, Cindy Hsu, Mohamad Tiba
Journal: Circulation (2024)

Introduction: Invasive arterial blood pressure can help optimize cardiopulmonary resuscitation due to the relationship of diastolic blood pressure with coronary perfusion pressure. The expulsion of blood from the thoracic cavity during chest compressions can result in retrograde blood flow during decompression causing incorrect extraction of diastolic pressure by monitors. To address this challenge, we evaluated several neural networks for automated extraction of diastolic blood pressure in swine cardiac arrest models. Methods: Fifty-two Yorkshire swine were anesthetized, instrumented, and subjected to 5 or 10 minutes of ventricular fibrillation or sham intervention. Cardiac arrest animals were resuscitated with mechanical chest compression and defibrillations, then monitored for 24 hours after return of spontaneous circulation. Systolic and diastolic locations were labeled for twenty seconds of data at each minute of resuscitation and each hour of monitoring. Several neural networks used in similar applications including ECG peak detection were built with Python’s TensorFlow library. A 70% train-test split was performed, and 5-fold cross validation was used to determine optimal hyperparameters. Models were evaluated on the final test set using F1 score. Results: The four models had similar performance on systolic peak detection with mean (SD) F1 scores of 0.99 (0.002) and 0.98 (0.002) for compression and non-compression waveforms respectively. The diastolic detection task was more difficult, with non-compression diastolic detection F1 score at 0.96 (0.006) and compression detection F1 score of 0.91 (0.01). Model size had a negligible relationship with F1 score. Compatible models were converted to the smaller TensorFlow Lite format and showed no drop in effectiveness despite a large reduction in memory requirement. Conclusion: Small models performed similarly to larger ones while requiring less memory. These models will allow easy analysis of compression effectiveness in cardiac arrest and are small enough to be integrated into a microcomputer onboard a portable monitor, enabling real-time resuscitation feedback. Additional data will be integrated into models, along with evaluation on human-derived waveform data.
Abstract Or107: Sulfatide-specific natural killer T cells regulate early inflammation and ameliorate post-cardiac arrest brain injury
Authors: Tomoyoshi Tamura, Changde Cheng, Ana Villasenor-Altamiran, Kohei Yamada, Kei Hayashida, Kohei Ikeda, Jaivardhan A. Menon, Xi Chen, Hattie Chung, Jiani Chen, Patrick Lawler, Rebecca Baron, Erin Bohula, David Morrow, Fei Chen, Louis Merriam, Alexandra Weissman, Michael Brenner, Xiang Chen, Fumito Ichinose, Edy Kim
Journal: Circulation (2024)

Background: Innate T cells have both deleterious and protective roles in a range of diseases. Natural killer T (NKT) cells are a major type of innate T cell, but their role and clinical relevance after cardiac arrest (CA) are undefined. Hypothesis: In patients after CA, an early increase in diverse NKT (dNKT) cells correlates with good neurological outcomes. dNKT cells improve outcomes after CA by reducing inflammatory responses in the brain. Aims: To investigate the clinical relevance of dNKT cells after out-of-hospital CA (OHCA) and their roles in a murine CA model. Methods: A clinical retrospective cohort study of complete blood cell counts with differentials after OHCA. Single-cell RNA-seq and flow cytometry of circulating T cells in OHCA patients. Good neurological outcomes were defined as a Cerebral Performance Category of 1 or 2 at 30 days post-CA. Single-nucleus RNA-sequencing(-seq) of hippocampal cells (50,332 nuclei), RT-PCR, and flow cytometry of the brain 24 hours post-CA in mice. Results: In a large OHCA patient cohort (N=1,955), the percentage of lymphocytes early (less than 12 hours) after CA was independently associated with good neurological outcomes (adjusted odds ratio [95%CI], 1.08 [1.03-1.14], P=0.005). Transcriptional profiling of T cells in OHCA patients at single-cell resolution showed an increase in an innate T cell-like NCAM1 + subset in patients with good neurological outcomes. This subset expressed cytotoxic, cytokine, and chemokine genes. Flow cytometry identified an early increase in circulating dNKT cells in patients with good neurological outcomes post-CA. In a murine model of CA, type II dNKT cells migrated to the brain after CA. NKT cell-deficient mice (Cd1d -/- ) had increased neuronal injury and mortality after CA. Cd1d -/- mice had increased molecular and cellular inflammation compared to wild-type mice 24 hours post-CA. Global transcriptomic analysis of murine brain at single-nucleus resolution indicated NKT cells suppressed inflammatory axes post-CA in multiple cell types, including astrocytes, microglia, and inhibitory neurons. Treatment with sulfatide (a lipid antigen for dNKT cells) improved neurological function after CA. Conclusions: Early abundance of dNKT cells was associated with good neurological outcomes after OHCA. dNKT cells are neuroprotective after CA by suppressing inflammatory axes in the brain. Immunomodulation of dNKT cells via endogenous lipids is a potential treatment approach after CA.