tbuckley/cabot-search huggingface dataset:
Abstract 4140343: Role of a novel protein phosphatase 2A activating drug in the regulation of late sodium current.
Authors: Nipun Malhotra, Michael Wallace, Hassan Musa, Sarah Takenaka, Mei Han, Xianyao xu, Thomas Hund, Natarajan Muthusamy, Peter Mohler, Mona El Refaey
Journal: Circulation (2024)

Introduction: The voltage-gated Na + channel, Na v 1.5, plays a leading role in the regulation of myocyte excitability and cardiac function. However, a small “late” component of Na v current I Na ( I Na,L ) increases in response to enhanced adrenergic conditions and is linked to fatal arrhythmias. I Na,L regulation is controlled by a host of proteins, in physiological and pathological states. However, little is known regarding pathways that negatively regulate I Na,L. Our previous work showed that protein phosphatase 2A (PP2A) modulation regulates Na v 1.5 activity but the field still needs molecules that selectively target PP2A in vivo. Hypothesis: Our newly identified PP2A activating drug will negatively modulate I Na,L via regulation of Na v 1.5 Ser571 phosphorylation. Methods: We isolated and cultured ventricular myocytes (VMs) from 3 months old C57Bl/6 mice. First, we treated the VMs with 2µM of drug for 1, 2, 3 and 4 hours to determine PP2A activity (n=4/group), later PP1 activity was assessed 3-hour post treatment of drug/DMSO in the presence of 5nM okadaic acid (n=4/group). Further, protein expression was evaluated after addition of drug/DMSO to the VMs for 3 hours, followed by 10 min treatment with 1 or 2µM Isoproterenol (Iso) (2µM Iso: n=3-7, 1µM Iso: n=4-5). Furthermore, I Na current-voltage relationship and I Na,L recordings comparing drug and DMSO treated mouse VMs were performed at baseline and after Iso (DMSO: N=8; n=15, drug: N=5; n=10, N: mouse, n: cell). Lastly, immunoblots were performed using heart lysates from control and post transverse aortic constriction surgery mice (n=4/group). Results: We observed an increase in PP2A activity 3 hours post drug treatment (p=0.0326), however no change in PP1 activity was observed in drug/DMSO treated VMs. We further confirmed a reduction in Na v 1.5pSer571 (2µM Iso: p=0.02, 1µM Iso: p=0.0398) levels with no changes in Ca v 1.2pSer1927 and total Na v 1.5 expression in drug treated VMs vs. DMSO. Patch clamp recordings revealed no significant changes in I Na current-voltage relationship, instead an increase in I Na,L was seen in DMSO treated VMs post Iso (p&lt;0.05). Drug treated VMs displayed a resistance to Iso-induced I Na,L prolongation at -35, -30, -25, -20, -15 and -10 mV voltage. Finally, increased expression of the PP2A inhibitor (I2PP2A/SET) was observed in failing heart vs non-failing control heart lysates (p=0.04). Conclusion: Our new compound activates PP2A via SET and specifically targets I Na,L in VMs.
Abstract 4140366: Diagnostic Stewardship to Improve Appropriate Use of Inpatient Echocardiography
Authors: Megan Welch, Molly Paras, Amber Moore, Jonathan Wing, Alyssa Letourneau, Tyler Tucker, Kristen Solemina, Judy Hung, Rory Weiner
Journal: Circulation (2024)

Background: Overuse of cardiovascular imaging, including echocardiography, is a form of low-value care contributing to waste in the US healthcare system. Historically, appropriate use criteria (AUC)-based educational programs and feedback reports have improved transthoracic echocardiography (TTE) ordering practices, but prior efforts have shown only modest and short-lived impact and have focused on the outpatient setting. Contemporary capacity and financial constraints highlight the importance of leveraging AUC to promote more efficient utilization of echocardiography resources. Methods: We conducted a prospective controlled cohort study testing an education-based diagnostic stewardship intervention to reduce rarely appropriate TTEs on inpatient medical services. AUC categorize TTE indications into three groups: appropriate (A), may be appropriate (mA), and rarely appropriate (rA). Modeled after successful antimicrobial stewardship programs, the intervention involved screening TTE orders from control and intervention units for appropriateness in real-time. For medical units in the intervention group, the diagnostic steward contacted ordering clinicians of those with mA and rA orders. The steward clarified order indications and made recommendations regarding the utility of the TTE. The ordering clinician chose to continue or discontinue the order. The primary outcome was the odds of rA TTEs in the intervention vs control groups. Results: Over 3 months, 150 TTEs were screened in the control group and 160 were screened in the intervention group. After initial screening, 8.8% (13) and 10.6% (17) were rA in the control and intervention groups, respectively. The stewardship intervention was employed for 17 rA TTEs and 13 mA TTEs. After the stewardship intervention, 17 of the rA TTEs remained classified as rA and 1 of the mA TTEs was reclassified as rA. Of the 18 rA orders, 16 were discontinued and 2 were completed (88% reduction). The stewardship intervention was associated with a significant reduction in completed rA TTEs when compared to the control group (OR = 0.15; 95% CI 0.03, 0.67; p = 0.005; Table). Conclusion: A stewardship intervention resulted in a significant decrease in completed rA inpatient TTEs among screened orders. In the era of capacity constraints, such a reduction represents a solution to improve clinical operations through targeted resource allocation. Future work to partially automate this initiative is important for scalability.
Abstract 4140268: Outcomes of Percutaneous Coronary Intervention in Patients With Major Depressive Disorder
Authors: Yazan Alkehef, Ramtej Atluri, omer alsheikh, Arshan Khan, sohail hassan, Nancy Mesih
Journal: Circulation (2024)

Introduction: Cardiac catheterization with percutaneous coronary intervention (PCI) has been the cornerstone of treatment in patients who present with myocardial infarction. Different outcomes have been studied in different patient populations. However, it is unclear if patients with major depressive disorder (MDD) have been receiving the appropriate treatment, or if patients with MDD who undergo PCI have different outcomes compared to the general population. Methods: Sample size was obtained from the National Inpatient Sample (NIS) from 2016 to 2019. We found 1,221,030 hospitalized patients who underwent PCI. These patients were further stratified based on the presence of MDD. A multivariate regression model was used to adjust for confounders and analyze the variables. Results: Only 5,380 (18%) patients with MI and MDD underwent PCI. There was no statistically significant difference regarding in-hospital mortality between patients with MDD who underwent PCI and those who underwent PCI but did not have MDD (2.7% vs. 3%; p=0.49). Patients with MDD who underwent PCI had a higher incidence of cerebrovascular accidents (CVA) compared to those who did not have MDD (1.8% vs 1.4%, p=0.0082). There was a higher incidence of in-stent restenosis (ISR) in patients who had MDD and underwent PCI compared to those who did not have MDD (7.1% vs. 4.9%; p=0.0013). When adjusted for age, comorbidities, gender, and hospital characteristics, patients with MDD had lower mortality than those without MDD with an odds ratio of 0.66. Conclusion: Although patients with MDD presenting with MI are a vulnerable population, it is likely that these patients are not always receiving the appropriate treatment. There is a higher incidence of cardiovascular events such as CVA, ISR, amongst other events. When adjusted for age, comorbidities, gender, and hospital characteristics, patients with MDD had lower mortality than those without MDD.
Abstract 4140276: Safety, Efficacy and Cardiovascular Benefits of Combination Therapy with Sodium-Glucose Co-Transporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists in Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Asma Mousavi, Shayan Shojaei, Hamidreza Soleimani, Davood Semirani-Nezhad, Pouya Ebrahimi, Ali Zafari, Rasoul Ebrahimi, Khatere Roozbehi, Anil Harrison, Mushabbar Syed, Polydoros Kampaktsis, Toshiki Kuno, Sean Heffron, Marc Samsky, Mani Khorsand Askari, Kaveh Hosseini
Journal: Circulation (2024)

Background: The potential benefits and risks of combination sodium-glucose co-transporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) therapy versus (vs.) monotherapy, remain a subject of debate to reduce metabolic and cardiovascular outcomes in patients with diabetes mellitus. This study aims to systematically review and meta-analyze the available evidence from randomized controlled trials (RCTs). Methods: A comprehensive search identified relevant RCTs comparing combination therapy with SGLT-2i and GLP-1RA to monotherapy or placebo. The primary outcome was the incidence of major adverse cardiovascular events (MACE) (all-cause mortality, cardiovascular mortality, stroke, myocardial infarction, and hospitalization for heart failure (hHF)). Secondary outcomes included changes in metabolic parameters and adverse events. Random-effects meta-analysis estimated risk ratios, mean difference, and 95% confidence intervals (CI). Results: The meta-analysis included 11 RCTs with 42,851 participants, of which 2,870 on combination therapy, and the rest on SGLT-2i (37.1%), GLP-1RA (20.1%) monotherapies or placebo (42.8%). Combination therapy had a significantly lower risk of MACE vs. GLP-1RA monotherapy (RR=0.81, 95% CI 0.65;1.00) and placebo (RR=0.73, 95% CI 0.61;0.88). Combination therapy also had a lower risk of hHF vs. GLP-1RA, SGLT-2, and placebo monotherapies (RR=0.37, 95% CI 0.22;0.65), (RR=0.37, 95% CI 0.19;0.75), and (RR=0.43, 95% CI 0.24;0.75), respectively. Combination therapy was showed greater weight loss and HbA1c reduction vs. SGLT-2i monotherapy (MD=-2.03, 95% CI -2.85;-1.21 and MD=-0.74, 95% CI -1.21;-0.27), respectively, while no difference vs. GLP-1RA monotherapy. Incidence of nausea and diarrhea was higher with combination therapy vs. SGLT-2i monotherapy (MD=3.34, 95% CI 1.74;6.43 and MD=1.75, 95% CI 1.10;2.77), respectively. Conclusion: Combination SGLT-2i and GLP-1RA therapy may provide superior cardiovascular, weight, and HbA1c outcomes vs. monotherapy, despite higher gastrointestinal adverse events. These results impact the management of patients with metabolic and cardiovascular diseases, and highlighting the need for further research to optimize combination therapy.
Abstract 4140544: Right ventricular free wall strain is superior to other methods of measuring right ventricular systolic function following invasive treatment for acute pulmonary embolism
Authors: Cathy Nguyen, Ethan Paliwoda, Denny Wang, Ahmad Mustafa, Lourdes Villarrubia Varela, Priti Mehla, Shankar Thampi, Arber Kodra, Victoria Roselli, Zein Kattih, Bushra Mina, Chad Kliger, Ythan Goldberg
Journal: Circulation (2024)

Introduction: Treatment for acute pulmonary embolism (APE) includes both noninvasive and invasive strategies. Transthoracic echocardiography (TTE) is the predominant test to assess right ventricular (RV) function following function, which is associated with adverse clinical outcomes. However, specific methods to measure RV function in clinical practice vary and have not been well-studied in the setting of APE. We sought to determine whether invasive treatment for APE was more effective than noninvasive treatment at achieving normal RV function as determined by various TTE measures. Methods: Data for 108 individuals treated for APE at our institution were retrospectively reviewed. All post-treatment TTE were performed within 72 hours of admission and prior to hospital discharge. There were no in-hospital mortalities. Logistic regression analysis was used to identify independent predictors of normal RV function defined as TTE-measured right ventricular-to-left ventricular diameter (RV/LV) ratio ≥ 0.9, tricuspid annular plane systolic excursion (TAPSE) ≥ 17.0mm, fractional area change (FAC) ≥ 35.0%, and right ventricular free wall strain (RVFWS) ≤ -20.0%. Independent variables chosen for analysis were: patient age, initial heart rate, syncope on presentation, presence of saddle PE on computed tomography, and having received invasive treatment for APE (catheter-directed thrombolysis, catheter-directed thrombectomy, or surgical thrombectomy). Results: Mean age was 61.5 (±17.7) years and 50.0% were male. Mean heart rate on presentation was 101 (±18) per minute. 16.7% presented with syncope and 23.1% were diagnosed with saddle. 55 (50.9%) patients were treated invasively, of whom 15 received catheter-directed thrombolysis, 36 mechanical thrombectomy, and 4 surgical thrombectomy. RV function data were as follows: RV/LV ratio = 0.95(±0.22), TAPSE = 18.9(±5.4) mm, FAC = 32.4(±4.4) %, RVFWS = -18.9 (±4.6) %. Invasive treatment was an independent predictor of normal RVFWS (p=0.04, odds ratio 2.6, 95%CI 1.1 - 6.8), but not of other measures of RV function. No other variables independently predicted any of the measures of normal RV function. Conclusion: An invasive treatment strategy for APE is more effective than a noninvasive strategy in achieving normal RV function as measured by RVFWS. Other measures were not associated with APE treatment type, suggesting that RVFWS should be the method of choice to assess RV function.
Abstract 4140571: High-Sensitivity Troponin Rules Out Risk of Myocardial Infarction and Death at 30 Days in Patients with Moderate and High HEART Score
Authors: Ethan Kramer, Nicolas Abchee, Rogina Rezk, Michelle Waples, Emily Meisel, Brandon Allen, Mohammed Ruzieh
Journal: Circulation (2024)

Introduction: The HEART score, developed over 15 years ago, aimed to guide the disposition decision for patients presenting to the emergency department (ED) with chest pain. A main concern for these patients is avoiding a missed myocardial infarction (MI). The original studies to develop the HEART score relied on an older generation of troponin assays, however high-sensitivity troponin assays are now widely used and have greatly enhanced the detection of MI. There is uncertainty in the utility of using the HEART score in the current era. Question: Can high-sensitivity troponin assays rule out risk of MI and death in patients with a moderate or high HEART score? Methods: We analyzed patients presenting to the University of Florida Shands Hospital, a tertiary medical center, with chest pain, high-sensitivity troponin I levels below the 99th percentile, and moderate or high-risk HEART score; 4-6 and 7+, respectively. Patients were recruited from June 2019 to December 2023. The HEART score was collected prospectively as part of our chest pain registry. We calculated the negative predictive value (NPV) for the outcomes of MI and cardiovascular death or death from an unknown cause at 30 days. Results: We included 1329 patients. The average age was 58.9 years and 52.7% were women. High sensitivity troponin I was negative (&lt;6 ng/L) in 892 patients and detectable but less than the 99th percentile (&lt;15 ng/L for women and &lt;20 ng/L for men) in 437 patients. A total of 1222 patients had moderate and 107 patients had high HEART scores. There were two (0.2%) MIs and one (0.1%) death in patients with negative troponin levels and no MI or death in patients with detectable levels below the 99th percentile. The NPV for negative or detectable troponin levels below the 99th percentile for both outcomes combined was 99.8% in the cohort overall, 99.8% in patients with a moderate HEART score, and 100% in patients with a high HEART score (Figure 1). Conclusion: In patients with chest pain and a moderate or high HEART score, negative or detectable high-sensitivity troponin levels below the 99th percentile have a high NPV in ruling out MI and death at 30 days. These findings can inform decision making in the ED for chest pain patients.
Abstract 4140639: Efficacy of Remote Patient Monitoring in Managing Hypertension in Federally Qualified Health Centers versus Primary Care Settings
Authors: Craig Flanagan, Brett Colbert, Kevin Davis, Wesley Smith
Journal: Circulation (2024)

Background: Remote patient monitoring (RPM) has proven highly effective in managing hypertension (HTN). A key strength of RPM lies in its ability to continuously monitor patients, especially those with limited access to traditional healthcare settings. Hypothesis: Do patients in Federally Qualified Health Centers (FQHCs) respond to RPM for HTN management as effectively as patients in traditional primary care settings (PC)? Goals/Aims: To compare the effectiveness of RPM between FQHC and traditional primary care populations. Specifically, we focused on patients who transmitted data at least 50% of the time, consistent with the CPT code for RPM billing, and who had been on the program for at least one year. Methods: Patients were equipped with cellular-enabled BP cuffs. Clinical staff met monthly with patients to review data and discuss lifestyle changes. Patients with an average SBP ≥140 mmHg or DBP ≥90 mmHg during the first 7 days, enrolled for ≥365 days, and transmitted data ≥50% of days, were analyzed. Data comparisons were made between the average of the first seven BP readings and the last seven BP readings. Results/Data: The PC group (n = 495) averaged 640 ± 280 days on the program, while FQHC patients (n = 429) averaged 599 ± 136 days. Both groups demonstrated significant improvements (p &lt; 0.0001) with RPM. PC patients reduced SBP from 150.7 to 135.2 mmHg (-15.5), and FQHC patients improved from 152.3 to 134.9 mmHg (-17.4). Baseline and final SBP readings were not significantly different between groups. DBP also markedly improved (P &lt; 0.0001): PC from 86.4 to 77.7 mmHg (-8.7 mmHg) and FQHC from 92.4 to 81.9 mmHg (-10.6 mmHg). FQHC patients had higher DBP at both baseline and study end (p &lt; 0.0001). Surprisingly, FQHC patients experienced a greater improvement in mean arterial pressure (MAP) compared to PC patients (-11.1% vs. -9.9%; p &lt; 0.05). Average transmission frequency was higher in PC patients (73.3%) compared to FQHC patients (70.3%; p &lt; 0.01). Conclusion: RPM significantly improves HTN management, leading to substantial reductions in blood pressure and MAP in both FQHC and primary care populations. These findings support RPM as an effective tool for managing hypertension remotely and enhancing health equity, making it a valuable strategy in diverse healthcare settings.
Abstract 4140502: Preventive Effects of Nitric Oxide Donors in Contrast-induced Nephropathy in Patients Undergoing Coronary Artery Angiography: An updated systematic review and meta-analysis of 13 randomized controlled trials.
Authors: Ahmed A. Ibrahim, Mohamed Rakab, Shehroze Tabassum, Ahmed Mazen Amin, Mohamed K Rifai, AlMothana Manasrah, Abdelrahman Mahmoud, Mohamed Abuelazm, Basel Abdelazeem, Ahmed gaber elsayed elsayed emara
Journal: Circulation (2024)

Background: Contrast-induced nephropathy (CIN) is associated with increased mortality and morbidity in patients undergoing coronary angiography (CAG) and percutaneous coronary intervention (PCI). We aimed to assess the latest evidence on the preventive effects of nitric oxide (NO) donors in CIN in patients undergoing CAG/PCI. Methods: We conducted a systematic review and meta-analysis of RCTs from PubMed, Web of Science, Scopus, Embase, and Cochrane searches until May 5th, 2024. Dichotomous data were pooled using risk ratio (RR), and continuous data were pooled using mean difference (MD), both with a 95% confidence interval (CI), using (R version 4.3). Results: Our analysis included 13 RCTs encompassing 3,550 patients. NO donors were significantly associated with a decreased incidence of CIN compared to placebo either as an oral administration (RR: 0.33 with 95% CI [0.26, 0.42], P&lt; 0.01) or IV infusions (RR: 0.56 with 95% CI [0.40, 0.78], P&lt; 0.01). Moreover, NO donors were significantly associated with decreased serum creatinine levels compared to placebo either as an oral administration (MD: -0.07 with 95% CI [-0.10, -0.04], P&lt; 0.01) or IV infusions (MD: -0.07 with 95% CI [-0.09, -0.04], P&lt; 0.01). In terms of safety, NO donors were significantly associated with a decreased incidence of MACE compared to placebo as an oral administration (RR: 0.64 with 95% CI [0.45, 0.89], P&lt; 0.01). However, there was no significant difference between NO donors as IV infusions and placebo in MACE (RR: 0.68 with 95% CI [0.38, 1.21], P= 0.18). Finally, NO donors were significantly associated with a decreased incidence of all-cause mortality compared to placebo as an oral administration (RR: 0.58 with 95% CI [0.36, 0.94], P= 0.03). However, there was no significant difference between NO donors as IV infusions and placebo in all-cause mortality (RR: 1.84 with 95% CI [0.40, 8.52], P= 0.44). Conclusion: NO donors as an adjunct therapy are associated with reduced incidence of CIN, and decreased serum creatinine levels either as an oral or IV administration. Also, it was associated with decreased incidence of MACE and all-cause mortality as an oral administration which make this simple low-cost intervention an important therapeutic option in patients undergoing CAG/PCI.
Abstract 4140514: Virtual Versus Center-Based Cardiac Rehabilitation: A Comparison of Outcomes and Cost
Authors: Neil Shah, Conor Banta, Andrea Berger, Andrea Hattenberger, Alex Zimmerman, Bryan Martin, Edward Wu, Usnish Majumdar, H Lester Kirchner, Martin Matsumura
Journal: Circulation (2024)

Introduction: Despite robust evidence supporting improved outcomes in eligible patients, cardiac rehabilitation (CR) remains underutilized. Virtual cardiac rehab (VCR) has been proposed as an alternative to traditional center-based CR (CBCR) to improve utilization rates. However, data supporting VCR efficacy and cost-effectiveness are lacking. In this study, we compared outcomes and cost of VCR vs. traditional CBCR. Methods: This retrospective cohort study compared VCR vs CBCR for Geisinger Health System, which primarily serves patients in rural Pennsylvania. CBCR data were collected from January 2018 to September 2023 and VCR data were collected from July 2021 to September 2023. Propensity scores were used to weight the observations and health outcomes were assessed using a weighted time-to-event analysis. Primary health outcomes measured were 1-year mortality rates, recurrent MI, all-cause hospital readmission, and emergency department visits, expressed as the incident rate ratio (IRR) of VCR:CBCR. Primary cost outcomes were analyzed as cost ratios of VCR:CBCR assessing total medical costs allowed, pharmacy costs, and total costs of care over the 12 months post-CR enrollment, while address data were used to compare the two modalities’ geographic footprints. Results: There were 3006 CR participants with mean age 67.7 years with 1017 (33.8%) women and 2924 (97.9%) white. A total of 2303 patients were enrolled in CBCR (76.6%) and 703 in VCR (23.4%). The VCR group was significantly older and had a significantly higher percentage of comorbidities including heart failure, diabetes and chronic pulmonary disease. Compared to CBCR, VCR was associated with a significant reduction in 1-year all-cause hospital readmission (IRR=0.616, p&lt;0.001) and 1-year ED admission (IRR=0.557, p&lt;0.001). The IRR of MI and all-cause mortality did not significantly differ between VCR and CBCR. In addition, VCR was associated with significant reductions in medically related (cost ratio=0.814, p=0.0144) and total costs (cost ratio=0.838, p=0.0176) in the year following initiation of CR. Conclusions: To our knowledge, the present study is the first to demonstrate both improvements in clinical efficacy and cost of VCR compared to CBCR. While this study’s retrospective design has limitations, it supports VCR as a viable addition to CBCR with at least comparable efficacy and cost, and as such, represents a key mechanism for improving access to and participation in CR for eligible patients.