tbuckley/cabot-search huggingface dataset:
Abstract 4118332: Suvorexant is associated with the reduced risk of feart failure rehospitalization in elderly patients with heart failure and insomnia
Authors: Tomoyuki Saito, Shuko Nojiri, Ryo Naito, Takatoshi Kasai
Journal: Circulation (2024)

Background: Research that compares the safety of orexin receptor antagonists and other types of hypnotics prescribed to elderly patients with heart failure (HF) and insomnia remains lacking. This study aimed to compare an orexin receptor antagonist, Suvorexant, with benzodiazepines or Z-drugs for insomnia treatment and investigate the risk of HF-related rehospitalization in elderly patients with HF and insomnia. Methods: A national administrative claims database from April 2008 to December 2020 was utilized and analyzed. The study population, consisting of 1,159,937 patients aged ≥65 years, was randomly sampled from the database. Patients were then selected based on specific inclusion and exclusion criteria. Exposures were identified based on the classification of the first prescribed hypnotic. The follow-up period was continued considering the prescription interval and grace period. The end of follow-up was censored based on multiple criteria, including outcome occurrences (i.e., HF rehospitalization) and hypnotic classification changes. Kaplan–Meier survival analysis and Cox proportional hazards models were used. Hazard ratios were adjusted by propensity scores derived from patients’ background factors. Results: The analysis included 1,858 elderly who had their first HF-related hospitalization. They were categorized into Suvorexant, benzodiazepines and Z-drugs groups (N=490, 606 and 762, respectively). The average age for all participants was 82.7 ± 7.6 years, which is similar across three groups. Kaplan-Meier curves indicated a higher trend of HF-rehospitalization risk for benzodiazepines and Z-drugs groups than for Suvorexant. The adjusted hazard ratios were 2.77 (95% confidence intervals [CI]: 1.17-6.52) for benzodiazepines and 2.98 (95% CI: 1.33-6.68) for Z-drugs. Conclusion: Compared with benzodiazepines and Z-drugs, the use of suvorexant for insomnia treatment in elderly patients with HF indicates a potential for the reduced risk of rehospitalization due to HF exacerbation. The results of this study provide valuable information for the selection of hypnotics in elderly HF patients with concurrent insomnia.
Abstract 4118959: Pulmonary Artery-Targeted Metformin-Loaded Nanocapsules Enhance Treatment of Pulmonary Arterial Hypertension
Authors: Ayako Chida-Nagai, Naoki Masaki, Hiroki Sato, Tatsuya Kato, Emi Takakuwa, Yoshihiro Matsuno, Atsushi Manabe, Atsuhito Takeda
Journal: Circulation (2024)

Background: Pulmonary arterial hypertension (PAH) remains a therapeutic challenge despite the availability of various medications. Metformin can be able to treat PAH but is associated with significant side effects. This study aims to enhance the efficacy and safety of metformin through a novel drug delivery system using low-dose metformin encapsulated in pulmonary artery-targeted nanocapsules. Methods: Metformin-loaded lung-targeted nanocapsules (MET nanocapsules) were synthesized using a specific lipid composition, including cationic lipids. The uptake and effects on cell viability were assessed in human pulmonary arterial smooth muscle cells (hPASMCs) from both healthy individuals and PAH patients. The therapeutic efficacy of MET nanocapsules was evaluated in a rat model of PAH. Safety was confirmed via serum biochemical tests in rats. Results: MET nanocapsules were successfully synthesized and demonstrated significant inhibition of PASMC proliferation. In the PAH rat model, MET nanocapsule treatment led to improved hemodynamic parameters, reduced right ventricular hypertrophy, and decreased pulmonary arterial medial thickening. Importantly, MET nanocapsules showed effective accumulation in the lungs of PAH rats. Conclusions: Intravenous administration of MET nanocapsules represents a safe and innovative therapeutic approach for PAH. This targeted delivery system has the potential to improve treatment outcomes while minimizing side effects and may have broader applications for other forms of pulmonary hypertension.
Abstract 4119658: Catheter Ablation for Ventricular Arrhythmias in Transthyretin Cardiac Amyloidosis: A Single Center Experience
Authors: Nader James Al-Shakarchi, Ikram Haq, Nicholas Tan, Martha Grogan, Angela Dispenzieri, Alan Sugrue, Omar Abou-Ezzeddine, Ammar Killu
Journal: Circulation (2024)

Background: Transthyretin cardiac amyloidosis (ATTR-CA) carries an elevated risk of developing ventricular arrhythmias (VA) but there remains limited evidence supporting the role of catheter ablation in this population. Purpose: To assess the safety and efficacy of catheter ablation for VA in ATTR-CA. Methods: An electronic database was used to identify all patients suspected of having ATTR-CA who underwent catheter ablation for VA at our institution between January 2010 and December 2023. Patients who did not meet the diagnosis of ATTR-CA and had a negative workup who underwent catheter ablation for ventricular tachycardia (VT) or premature ventricular contractions (PVCs) were used to form a control group matched for age, sex and left ventricular ejection fraction at a ratio of 2:1. Results: 20 controls and 10 cases of ATTR-CA were identified. Examining the two groups at baseline (Table 1), the mean age at index ablation was 67.7±7.0 and 68.6±8.1 years (p=0.359), mean follow-up time was 4.1±3.1 and 4.2±2.6 years (p=0.494), and the proportion of males was 100% and 90% respectively. The ATTR-CA group had a significantly higher proportion of chronic kidney disease (90% vs. 50%, p=0.032) and prior stroke or thrombotic events compared to the control group (50% vs. 10%, p=0.026) with similar CHA 2 DS 2 VASc scores (4.2±1.6 vs. 3.8±1.3, p=0.233). Both groups had comparable left ventricular ejection fraction (41.4%±14% vs. 46.9%±15.2%, p=0.173), VT/PVCs at presentation (40%/60% vs. 25%/75%, p=0.77), use of antiarrhythmics (70% vs. 60%, p=0.592), and high proportion of atrial fibrillation/flutter (70% vs. 90%, p=0.168). Procedural (261.2±101.2 vs. 265.7±125.6 mins, p=0.449) and total energy delivery time (1442.9±1509.1 vs. 1744.6±956.2 secs, p=0.296) was not significantly different in the two groups. Both groups had a significant decrease in PVC burden postablation with a reduction from 26.8% to 3.8% (p=0.024) and from 27.1% to 13.6% (p=0.028) in the ATTR-CA and control group respectively. A downward trend was seen in antitachycardia pacing events for VT postablation in the ATTR-CA (14.7±9.8 vs. 5.3±6.7, p =0.184) and control (193±387.6 vs. 0.67±1.2. p=0.139) groups. No major complications occurred after ablation (Table 2). Mean time to recurrence post-index ablation was similar between both groups (1620.4±483.8 vs. 1498.8±291.4 days, p=0.987, Figure 1). Conclusions: Catheter ablation appears to be safe and effective for VT and PVCs in patients with ATTR-CA.
Abstract 4117479: INTERPRETABLE PREDICTION OF HOSPITALIZATION COSTS FOR PATIENTS WITH ISCHEMIC HEART DISEASE USING NETWORK ANALYTICS AND MACHINE LEARNING
Authors: 亚军 薛
Journal: Circulation (2024)

Background: Ischemic heart disease (IHD) represents a significant global health challenge, imposing a considerable social and economic burden on individuals and healthcare systems worldwide. To optimize medical resource allocation and better serve populations, accurately predicting healthcare costs is paramount. Methods: This study proposes an interpretable feature extraction method based on network analytics to improve the prediction of IHD hospitalization costs. A diagnosis-procedure concurrence network is constructed, and a graph kernel-based approach is utilized to capture and encode information on diseases and treatments. The study introduces a hospitalization cost prediction model that utilizes a diagnosis-procedure concurrence network to extract features that strike a balance between predictability and interpretability. Results: Our model demonstrates superior performance, considering that the average cost for all patients in the HQMS dataset is approximately 20,000 CNY, whereas the average cost for our IHD patient dataset is 37,853 CNY. This indicates the effectiveness of our approach in predicting hospitalization costs for a specific patient population with complex treatment options such as IHD. Conclusion: This study aims to develop an interpretable and precise model for forecasting hospitalization costs of Ischemic Heart Disease (IHD) patients in China. It achieves this goal by integrating machine learning with network analytics and incorporating cost ratio features.
Abstract 4118084: Targeting Monoamine Oxidase B in Dystrophic <i>mdx</i> Hearts Dampens Inflammation and Fibrosis
Authors: Francisca Venegas, Francesca Gasparella, Ricardo Sanchez Rodriguez, Francesca Fontana, Libero Vitiello, Marcella Canton
Journal: Circulation (2024)

Background: Cardiomyopathy is a major cause of death for Duchenne muscular dystrophy (DMD) patients. Current treatments cannot prevent cardiac tissue remodeling. Oxidative stress, inflammation and fibrosis are early events in DMD, preceding heart dysfunction. Monoamine Oxidase B (MAOB), which forms H 2 O 2 by oxidizing amines, is overactivated in inflammatory conditions and overcomes cell antioxidant defenses, thus altering redox homeostasis and eliciting harmful effects. We showed that targeting MAOB with inhibitors (iMAOB) improves skeletal muscle function in dystrophic mice by lowering oxidative stress, and reduces inflammation in murine models of sepsis and arthritis by dampening NF-kB, a redox-sensitive transcription factor. Aim: We explore the therapeutic potential of iMAOB to alleviate cardiomyopathy using dystrophin-deficient mdx mice. We hypothesize that iMAOB treatment could dampen oxidative stress, inflammation and fibrosis in dystrophic mdx hearts by modulating the phenotype of cells that are crucial in cardiac remodeling. Methods: Three-month-old mdx mice, that already show signs of fibrosis but no cardiac dysfunction, were orally treated with iMAOB or vehicle for one month (n≥ 6). Heart ventricular mononucleated cells were obtained by enzymatic digestion. Myeloid, endothelial and fibroblast cells were isolated by cell sorting by FACS and analysed by RT-PCR. Oxidative stress, inflammation and fibrosis were measured in whole tissue by immunohistochemistry. Results: The expression of proinflammatory and profibrotic genes was markedly increased in myeloid [Interleukin (Il)-1b, Il-6, Tgf-b and Spp1, the gene coding for osteopontin], endothelial [Il-1b, Il-6, mmp2 and nos3] and cardiac fibroblast cells [Tgf-b, Spp1, Timp1 and Col1] isolated from mdx hearts, as compared to wild type mice. All these genes were significantly dampened by iMAOB treatment. In parallel, once again iMAOB treatment blunted the increase in oxidative stress, inflammation and fibrosis observed in mdx cardiac sections. Of notice, the differences were not linked to changes in the percentage of the various cell types, as they were unmodified amongst wild type, mdx and iMAOB-treated mdx hearts. Conclusions: We show that iMAOB can positively affect the phenotype of cells that are important in cardiac tissue remodeling. Our data suggest that iMAOB can be a viable therapeutic tool in DMD cardiomyopathy. As iMAOB are already in clinical use, such approach could be easily translated to patients.
Abstract 4117640: Thirty-Year Prevalence and Prognosis of the Cardiovascular-Kidney-Metabolic Syndrome in U.S. Females and Males
Authors: Hongwei Ji, charumathi sabanayagam, Kunihiro Matsushita, Ching-Yu Cheng, Tyler Hyungtaek Rim, Bin Sheng, Huating Li, Yih Chung Tham, Susan Cheng, Tien Wong
Journal: Circulation (2024)

Background: The American Heart Association recently published guidelines on how to clinically identify and categorize individuals with cardiovascular-kidney-metabolic (CKM) syndrome. The extent to which CKM syndrome prevalence and prognosis differ by sex remain unknown. This study aimed to examine the impact of sex on trends in prevalence over 30 years and long-term prognosis of the CKM syndrome in the US. Methods: We analyzed nationally representative NHANES 1988-2018 data collected from 33,868 US adults (age ≥20 years) who were under surveillance for all-cause mortality through December 31, 2019. We examined sex-specific prevalence of CKM syndrome, and sex-specific CKM associations with all-cause mortality. Results: Of the 33,868 adults studied, the mean±SD age was 48.4±18.3 years with 52% female and 56% non-White. Overall prevalence of CKM syndrome increased steadily from 1988 to 2018 in both sexes, with a larger temporal rise in prevalent Stage 3 CKM seen for males (from 18.9% to 22.4%) compared to females (from 13.9% to 15.2%) ( Figure 1 ). Over a median follow-up of 13.3 years, there were 8745 deaths. In multivariable cox-regression analysis, worsening CKM severity was associated with all-cause mortality (P&lt;0.001 for both sexes), with greater magnitudes of risk seen in females (HR=1.24 to 3.33) compared to males (HR=0.85 to 2.60) across all stages (LRT χ 2 =19.0, P interaction &lt;0.001); results were similar for cardiovascular mortality (LRT χ 2 =22.3, P interaction &lt;0.001) ( Table 1 ). Conclusions: Females, compared with males, exhibited a lower prevalence of CKM stage 3 but experienced excess mortality risk across the spectrum of multi-system CKM dysfunction. These findings underscore the importance of identifying mechanisms underlying joint cardiovascular, renal, and metabolic systems pathophysiology to close a potentially widening sex disparities gap in multi-organ disease risk.
Abstract 4115642: Resonance Sonomanometry in an Early Prototype Device Effectively Measures Continuous, Noninvasive Blood Pressure
Authors: Alaina Rajagopal, Raymond Jimenez, Matt Fu, Dominic Yurk, Justin Yanuck, William Dempsey, Aditya Rajagopal
Journal: Circulation (2024)

Background: Nearly half of American adults have hypertension; however, reliable, continuous, noninvasive blood pressure (BP) measurement (cNIBP) for inpatient and outpatient use is not currently available. This study evaluated a new method for cNIBP measurement called resonance sonomanometry (RSM). RSM derives blood pressure using first-principles physics, is applicable to any artery, and requires no calibration, blood vessel deformation, or dependence on demographic inputs. Methods: A prospective, observational feasibility study was undertaken to compare carotid artery BP measurements with a prototype ultrasound-based cNIBP device incorporating RSM, to arterial catheter BP measurements in the radial arteries of 60 test subjects. Catheter measurements were obtained from a distal peripheral artery (radial), oscillometric cuff from the brachial artery, and RSM was obtained from a central artery (carotid). This study was the first-in-human study for the RSM method in comparison to arterial catheters. Results: RSM-induced arterial resonance was observed in all tested subjects. For each of the subjects, the arterial resonant frequency increased with increasing BP during systole, and decreased with diastole (consistent with the cardiac cycle), as predicted by the physical model. RSM-derived BP traces were qualitatively similar to catheter data, exhibiting features such as the dicrotic notch. The RSM method yielded similar diastolic BP (DBP), but lower systolic BP (SBP) compared to the arterial catheter, likely due to expected peripheral pulse amplification. RSM DBP was not significantly different from the catheter (+1.5mmHg, p = 0.187), while BP cuff DBP was significantly different from the catheter (−4.3mmHg, p=0.002). There were significant differences in the catheter to RSM SBP (34.1 mmHg, p &lt; 0.01), consistent with the aforementioned expectations from a central-versus-peripheral continuous pressure measurement. Conclusions: RSM is a novel BP measurement technique that could enable cNIBP measurements with accuracy required in hospitals. While the data are promising, significant future work remains. The study was meant to test the RSM method, not the device or form factor. Consequently, the form factor will need to be improved prior to clinical use. The prototype was designed for manual operation; thus, future work will also be needed to enhance the ability of the device to autonomously locate and track the artery for ease of use.
Abstract 4115634: Potential Role for Circadian Disruption in Acute Kidney Injury-driven Cardiovascular Disease
Authors: Mark Segal, Yanpeng Diao, Lauren Douma, Gene Crislip, Yuanqing Lu, Shuhong Han, William Clapp, Michelle Gumz
Journal: Circulation (2024)

Background/Hypothesis: Circadian disruption and AKI, even if kidney function recovers, are linked to an increased risk of CVD and death. We explored the hypothesis that AKI was associated with CVD through circadian disruption. Approach: Sixteen ~25-week-old PER2::Luciferase (a real-time reporter of circadian rhythm) C57BL/6J male mice had micro-clamps applied to both renal pedicles for ~26 minutes to produce a recoverable AKI. Three animals underwent a sham procedure. Three animals had to be euthanized all others had serum creatinine (Scr) measured on day 2. Twelve weeks after surgery, all animals (n=13) were euthanized. Results: The sham group's day 2 Scr (n=3; mean 0.10 [range 0.08 - 0.15]) was unchanged from baseline (0.11 [0.07 - 0.18]). Based on the day 2 Scr, 3 mice were classified as having mild/moderate AKI (Scr increased ≤ 3-fold) (0.16 [0.08 - 0.20]) and 7 as having severe AKI (Scr increased &gt; 3-fold) (0.98 [0.26 - 1.93]). By 12 weeks post-AKI, the Scr (0.16 [0.1 - 0.2 mg/dl]) of all animals returned to a level statistically similar to baseline. Immunohistochemistry demonstrated that 6 of 7 mice with severe AKI had atherosclerotic-like lesions in the aortic root (A), sinus, or coronaries (B): 4 mice had lesions averaging 9,754.7 µm 2 and 2 mice had coronary artery lumen narrowing averaging 56.2%. Similar lesions were found in 1 of 3 mice with mild/moderate AKI, but no lesions were found in the sham animals (C). The lesions had CD45+ cells on their surface and in the adventitia (A inset), but were devoid of CD68+ and SMC alpha-actin+ cells. In the neointima, SMC alpha-actin+ cells predominated (B inset). Mouse liver, lung, adrenal gland, renal cortex, outer and inner medulla were collected at 15:00 and analyzed for 5 days by Lumicycle. Circadian rhythms were evaluated with JTK_CYCLE. No apparent AKI-dependent differences were observed in the liver, lung, adrenal, or renal outer medulla. However, the amplitude of renal inner medulla rhythms decreased with AKI (P = 0.008), while the amplitude of renal cortex increased with AKI (P = 0.01, E&amp;F). Conclusions: This is the first report of an AKI model resulting in atherosclerosis-like lesions in wild-type mice without the need for a high-fat diet, genetic manipulation, or further provocation. The lesions were associated with a disruption of the intrarenal circadian rhythms. We will discuss the implications of this research as well as the metabolic consequences of the circadian disruption.
Abstract 4115816: Enhancing Cardiogenic Shock Management: Insights from MCS utilization and Patient Outcomes
Authors: monika karki, Pramod Bhattarai, Riya Mohan, Yordanka Reyna
Journal: Circulation (2024)

Cardiogenic shock (CS) remains a challenge with high mortality rates despite advances in treatment modalities. This study investigates the utilization and impact of mechanical circulatory support (MCS) devices, including intra-aortic balloon pump (IABP), Impella, and Extracorporeal Membrane Oxygenation (ECMO) on patient outcomes in CS management. A retrospective analysis was performed using National Inpatient Sample data (2017 to 2019). Inclusion criteria included patients aged ≥18 years with primary diagnosis of CS using ICD10(R570). Multivariate regression analysis was used to assess MCS duration, mortality, length of stay (LOS), and costs. Among 462,685 included patients, 38% were female, with a mean age of 66 years. Majority were White (67%), followed by Black (16.5%), and Hispanic (9%). IABP was utilized in 13% of cases, Impella in 6%, and ECMO in 0.9%. No significant difference was observed in MCS placement between weekdays vs weekends. However, weekend admissions showed higher mortality rates with an odd ratio (OR) of 1.06(p &lt;0.00, CI 1.03-1.09), particularly among females OR 1.25(p&lt;0.00, CI 1.22 – 1.289). Urban non-teaching hospitals exhibited highest mortality rate, followed by Urban teaching. ECMO was associated with highest mortality OR 2.08(p &lt; 0.00, CI 1.93-2.82), followed by Impella OR of 1.47 (p &lt; 0.00, CI 1.37 – 1.59), and IABP OR 0.723 (p &lt; 0.00, 0.685-0.765). LOS was lowest in Impella group, followed by IABP, while ECMO showed non-significant LOS increase. Mean total charge varied among MCS groups with ECMO being highest. The findings highlight several important aspects of CS management. Elevated mortality rates during weekend admissions suggest potential disparities in care access or delivery, necessitating investigation and interventions to ensure consistent quality of care throughout the week. Increased mortality among females, variations across different hospital settings, impact of MCS devices on LOS and costs emphasize the need for tailored approaches to enhance patient outcomes and resource utilization efficiency.
Abstract 4117406: The Safety and Efficacy of Surgical Cardiac Sympathetic Denervation for Ventricular Arrhythmias: An Updated Systematic Review&amp;Meta-Analysis
Authors: Daniel Hanna, Reza Karimianpour, Nicole Mamprejew, Christopher Fiechter, Juan Sierra, Dhiran Verghese, Elsy Navas, Dinesh Sharma
Journal: Circulation (2024)

Objectives: This meta-analysis sought to explore the long-term arrhythmic outcomes of cardiac sympathetic denervation (CS) by measuring event rates of recurrent ventricular arrhythmias (VA) and implantable cardiac defibrillator shocks (ICD) post CSD. Background: The role of sympathetic nervous system in the beginning and continuation of ventricular arrhythmias (VAs) is well known. CS has been associated with improved arrhythmic outcomes in patients with refractory ventricular arrhythmias. However, whether CSD lowers shock event rates after the procedure is still uncertain and therefore, we performed a systematic review and meta-analysis to evaluate this. Methods&amp;Materials: A comprehensive literature search was performed at Medline and Embase until March 2023. Our primary outcome was event rate of ICD shocks at 30 days, 90 days, and 1 year following CS. All analysis was conducted using Comprehensive Meta-Analysis software. Results: The initial search found 1,324 articles. After all articles were examined, a total of 29 studies fit our criteria. ICD shocks 1 year post CSD had a pooled event rate of 66.5% with a 95% confidence interval (CI) of 57.7% to 74.3% and the I-squared (I2) statistics. ICD shocks at 6 months had an event rate at 61.7% with a 95% confidence interval of 53.3% to 69.4% with I2 at 46. VA in one year post CSD had a pooled event rate of 62.5 with a 95% with a CI of 53.3% to 69.1% and I2 at 22%. At 6 months the event rate was 64.2 with a 95% CI of 56.3% to 71.4% with I2 at 33% Mortality from cardiac arrhythmia and classified 0-30 days (short term), 21-364 days (medium term), and &gt;365 days (long term). The pooled event rate for short term morality was 6.8% with a 95% CI of 4.2%-11.0% with I2 at 0%, medium term was 5.2% with a 95% CI of 2.9% to 8.9% with I2 at 0%, and long term was 5.0% with a 95% CI of 2.7% to 9.2% and I2 at 0%. Conclusion: CSD may be an alternative form of therapy that reduces shock event rates and recurrent VA in patients that are refractory to ablation and medical therapy. However larger prospective studies are needed to further evaluate the usefulness and safety of CSD.