tbuckley/cabot-search huggingface dataset:
Abstract 4136023: Eligibility and Barriers of Mavacamten Therapy in Patients with Hypertrophic Cardiomyopathy: A Retrospective Analysis
Authors: Sarah Jiang, Krish Sardesai, Abdulrehman Yousaf, Nicholas Norgard, TALAL ASIF
Journal: Circulation (2024)

Background: Hypertrophic Cardiomyopathy (HCM) is a common genetic heart disorder characterized by the thickening of the myocardium. Mavacamten has emerged as a novel medication for targeted therapy in HCM patients, but its adoption faces multiple hurdles. This study aims to evaluate the eligibility of HCM patients for Mavacamten treatment based on certain clinical criteria and to promote consideration of potential barriers patients face in obtaining this medication. Methods: We conducted a retrospective analysis of 115 HCM patients at Truman Medical Center that included demographic data, clinical characteristics, and treatment histories. Patient eligibility for Mavacamten was determined based on ejection fraction (EF) &gt; 55%, symptomatic obstructive HCM, and intolerance to first-line therapy (beta-blockers, calcium channel blockers). Statistical analysis was performed using standard deviation and mean comparisons to estimate the proportion of eligible patients. Results: Out of 115 patients, 96 patients have an EF&gt;55%. 76 patients (66.1%) have a clinical heart failure diagnosis. 94 patients (81.7%) are taking beta-blockers. 49 patients (42.6%) have uncontrolled hypertension indicated by blood pressure &gt;140. Considering these factors, 49 (42.6%) met the clinical criteria for Mavacamten treatment. Of these patients eligible to receive Mavacamten treatment, only one patient was actively taking Mavacamten. The most common obstacles to receiving the drug included lack of insurance coverage, high medication cost, and limited awareness among healthcare providers regarding new treatment options. Conclusion: While a considerable proportion of HCM patients qualify for Mavacamten based on clinical criteria, external factors significantly impede access to this potentially life-altering treatment. Efforts should address this treatment gap through raising awareness to healthcare professionals and improving insurance coverage. This will enhance patient access to Mavacamten, ultimately improving outcomes in HCM management. This study summarizes the eligibility and obstacles to Mavacamten in a sample of HCM patients, emphasizing the need for systemic changes to facilitate access to advanced therapies.
Abstract 4135923: Predictive Value of Supraventricular Tachycardia on Ambulatory ECG Monitoring for Recurrent Atrial Fibrillation Post-Catheter Ablation
Authors: Ghazal Sanadgol, Adham Ramadan, Tristan Alfie, Mohammad Hosein Yazdanpanah, Acile Nahlawi, Leon Ptaszek, Jeremy Ruskin
Journal: Circulation (2024)

Introduction: Established predictors of recurrent atrial fibrillation (AF) following catheter ablation (CA) have not incorporated findings on post-CA ambulatory ECG monitoring (AECG). Aims: This study examined the predictive value of supraventricular tachycardia (SVT) detected on 7–14-day AECG for recurrent AF within one year post-CA. Methods: This single-center retrospective study included a select subset of patients who underwent CA for AF between 2015 and 2023 and had AECG monitoring within the first year post-CA. SVT presence and characteristics on AECG were analyzed.Data on demographics, AF risk factors, and AF recurrences were extracted from electronic health records. ROC curves determined SVT episode thresholds. A multivariable regression model included established risk factors and SVT thresholds, and best subsets regression identified predictors of AF recurrence. Results: Of 7,481 patients undergoing CA for AF, 1,245 were monitored within one year post-CA. Among this subset, 439 (35.26 %) had recurrent AF during the first year post- CA. Of the 439 patients with recurrent AF, 99 had AECG monitoring before recurrence. These 99 patients were compared with the 672 patients with no AF recurrence. Average duration of AECG monitoring for the entire cohort was 11±2.7 days. Mean SVT episodes per day ≥4.6 and total number of SVT episodes ≥14.5 were significantly associated with recurrent AF (OR =1.99, P =0.030, and OR =2.77, P =0.019, respectively). Significant predictors of AF recurrence were female gender, heart failure, confirmed SVT, cardioversion before ablation, mean SVT episodes per day, and total SVT episodes on AECG. Conclusion: High burden of SVT on AECG monitoring (defined in this study to be ≥4.6 episode per day or ≥14.5 total episodes per monitoring period) was significantly associated with AF recurrence. Longitudinal studies in larger unselected populations are needed to confirm these results.
Abstract 4136448: A Novel Cardiomyocyte Targeting Peptide Enhances Calcium Handling
Authors: Jack Lopuszynski, Jingyu Wang, Roy Dyer, Daniella Sahagun, Maliha Zahid
Journal: Circulation (2024)

Introduction: Intracellular calcium handling plays a central role in cardiac contractility and relaxation. Genes such as the Ca 2+ -ATPase pump (SERCA2a) and the Dihydropteridine reductase (DHPR) enzyme are especially important in the cycling of intracellular calcium. As prior research has established a link between treatment with our cardiac targeting peptide (CTP: a 12-amino acid, cardiomyocyte-specific cell penetrating peptide) and upregulation of calcium-handling genes such as SERCA2a and DHPR, we hypothesized that treatment with our novel hybrid cardiac targeting peptide (hCTP: positions #3 and 11 replaced with the D-enantiomer form of the amino acids) will improve intracellular calcium handling in human cardiomyocytes (CMCs) by increasing expression of key calcium handling genes instrumental in sequestering calcium in diastole and lowering cytosolic levels. Methods: To test hCTP’s calcium handling abilities, CMCs were plated on day 1 and allowed to settle for 24 hours, after which they received daily treatment with various concentrations of hCTP (1-25µM) for three days. On day 5, cells underwent either intracellular calcium measurements using the FLIPR 6 Calcium assay or were prepared for western blotting. Western blotting was performed to determine the protein concentrations of SERCA2a and DHPR, as compared to a GAPDH control. To test hCTP’s intrinsic calcium handling abilities, various concentrations of hCTP were mixed with a constant amount of elemental calcium dissolved in water. After 20 min at 37 o C, the concentration of free Ca 2+ was measured with an ABL90 Flex Plus radiometer. Results: In CMCs, treatment with hCTP led to a decrease in cytosolic calcium in a dose dependent fashion; concentrations as low as 1µM led to a significant decrease in cytosolic calcium (p&lt; 0.0001 for all groups). Western blots performed on the treated CMCs revealed an increase in expression of both DHPR and SERCA2a, normalized to GAPDH control. Outside of the cellular environment, hCTP did not appear to display inherent calcium sequestring properties, suggesting that improvements in calcium handling are due to upregulation of gene expression. Conclusion: hCTP appears to lower cytosolic calcium and improve calcium handling through upregulation of SERCA2a and DHPR. Our data indicates that hCTP is worth pursuing as a stand-alone, cardio-selective therapy for cardiomyopathies involving calcium mishandling.
Abstract 4135975: Anticoagulation versus Antiplatelets in Coronary Artery Ectasia and Acute Coronary Syndrome: A Systematic Review and Meta-analysis
Authors: Sarai Hernandez Pastrana, Mohamed Doma, Syeda Rubab Fatima, Maya Hemdanieh, Mangesh Kritya, Wilbert Huang, Zahra Naji, Shanmukh sai pavan Lingamsetty, Douglas Mesadri Gewehr, Ximena Latapi Ruiz Esparza, Felipe Martignoni, Diego Araiza
Journal: Circulation (2024)

Introduction: Coronary artery ectasia (CAE) is a rare but well-recognized anatomical abnormality of the coronary arteries with a prevalence of up to 9% in patients presenting with acute coronary syndrome (ACS). While anticoagulants have been suggested to reduce recurrent events, the optimal antithrombotic therapy in CAE and ACS remains unclear. Research Question: What is the comparative effect of anticoagulation therapy versus no anticoagulation in patients with CAE and ACS receiving background antiplatelet therapy? Goals: To perform a systematic review and meta-analysis evaluating the efficacy of anticoagulation in preventing major adverse cardiovascular events (MACE) among patients with CAE and ACS. Methods: We searched PubMed, Embase, and Cochrane to identify studies comparing the use of anticoagulants versus no use of anticoagulants as part of the antithrombotic therapy in patients presenting CAE and ACS, and reported MACE. Statistical analysis was performed using R version 4.2.2 adopting the Mantel-Haenszel random-effects model. Heterogeneity was assessed using Cochrane's Q statistic and Higgins and Thompson’s I2 statistics. Pooled risk ratios were used to evaluate the effectiveness of anticoagulant therapy in CAE and ACS. Results: We included 3 studies, including 1 randomized controlled trial and 2 observational studies, comprising a total of 441 patients, of whom 162 (36.7%) received anticoagulants, including vitamin K antagonists (warfarin and acenocoumarol) or direct oral anticoagulants (rivaroxaban, apixaban, and dabigatran). Time of follow-up ranged from 12 to 52 months, mean age was 57.9 ± 11.4 years, and 388 (87.9%) were male. We found no significant difference in MACE between patients who received anticoagulation and patients who did not (RR 0.64; 95% CI 0.31, 1.32; p=0.22; I2 = 0%). Additionally, there was no difference in the risk of re-infarction (RR 0.71; 95% CI 0.43, 1.18; p=0.19; I2 = 0%). Finally, there was no significant difference in risk of bleeding between both groups (RR 1.41; 95% CI 0.70, 1.85; p=0.19; I2 = 0.59%). Conclusion: Our findings suggest that, among patients with CAE and ACS, anticoagulation does not reduce the risk of MACE or re-infarction as compared with no anticoagulation.
Abstract 4136210: Meta-Analysis of Efficacy and Safety in DAPT De-escalation: Transitioning from Ticagrelor to Clopidogrel in Acute Myocardial Infarction Following Percutaneous Coronary Intervention at twelve-Month Follow-Up
Authors: Hashim Talib Hashim, Ahmed Qasim Mohammed Alhatemi, Sania Riaz, Zahraa Hussein Ali, Mohamed K Rifai, Humza Saeed, Shehroze Tabassum, Fatimah Abdullah Sulaiman, Ahmed Dheyaa Al-Obaidi, Omar Saab
Journal: Circulation (2024)

Background: In the management of acute myocardial infarction (AMI) following percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) plays a crucial role in preventing recurrent ischemic events. Recent studies have explored the feasibility and safety of de-escalating DAPT from ticagrelor to clopidogrel. Methods: We conducted a systematic review and meta-analysis by searching several databases, including Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, MEDLINE (including MEDLINE InProcess) (OvidSP), Web of Science, Embase (OvidSP), and Scopus. We assessed the risk of bias using the ROB2 Cochrane tools for randomized controlled trials (RCTs). The analysis was performed using RevMan Cochrane software. Results: A total of ten studies including observational and clinical studies involving N=18,001patients (11,458 de-escalated from ticagrelor to clopidogrel after 12 months and 6,543 remained on ticagrelor after 12 months post-PCI) were included. There was no difference in the risk of all-cause death (RR 0.98; 95% CI 0.69 to 1.38; p=0.90), cardiovascular death (RR 1.09; 95% CI 0.68 to 1.74; p=0.73), myocardial infarction (RR 0.90; 95% CI 0.71 to 1.14; p=0.37) and stroke (RR 0.81; 95% CI 0.50 to 1.32; p=0.41) between the two groups. Conclusion: In conclusion, transitioning from ticagrelor to clopidogrel in acute myocardial infarction following percutaneous coronary intervention appears to be a feasible strategy for de-escalating dual antiplatelet therapy (DAPT). While maintaining efficacy in preventing adverse cardiovascular events, such as stent thrombosis, this approach may mitigate bleeding risks associated with prolonged ticagrelor use.
Abstract 4136614: The design of novel therapeutics that target the L-type calcium channel to prevent hypertrophic cardiomyopathy
Authors: Livia Hool, Teagan Er, Daniel Reinke, Alice Francis, Tanya Solomon, Helena Viola, Henrietta Cserne Szappanos, Caitlyn Richworth, Khanh Vu, Cathy Jenkins, Juan Camacho Londono, Padmapriya Ponnuswamy, Ciaran McFarlane, Filip Van Petegem
Journal: Circulation (2024)

Background: Hypertrophic cardiomyopathy (HCM) is an inherited autosomal dominant disease of the sarcomere. Pathogenic features include ventricular hypertrophy, increased myofilament calcium sensitivity, myocardial fibrosis, and diastolic dysfunction. At the level of the myocyte there is cytoskeletal disarray, hypercontractility and altered mitochondrial function. Mitochondrial dysfunction is considered to be a key driver in HCM pathology. Research question: We previously demonstrated that the L-type Ca 2+ channel plays a role in the development of HCM facilitated by a structural-functional communication with mitochondria that can be regulated via the alpha interaction domain (AID) of the channel. In search of a preventative HCM therapy, we explored the efficacy of amino acid peptide variants that correspond to the AID of the cardiac L-type Ca 2+ channel. Methods and Results: Consistent with in silico predictions , competition binding assays confirmed that 4 variant peptides bound with higher affinity to the beta subunit than the AID peptide. In vitro studies confirmed that 3 of the 4 peptides could decrease the characteristic hypermetabolic state in myocytes isolated from a murine model of human HCM ( cTnI-G203S ). In vivo treatment of cTnI-G203S mice with peptide variants prevented the development of HCM and the development of fibrosis, in the absence of alterations in blood pressure, or kidney and liver function or changes in behaviour. Of note, the peptide variants also significantly improved contractile function. Similar effects were measured in αMHC 403/+ mice expressing the MYH6 mutation. Conclusions: Here we describe a first in class therapy that uniquely targets the L-type Ca 2+ channel to modify mitochondrial function and prevent hypertrophic cardiomyopathy. The peptides may be effective for treatment of HCM broadly because the mechanism of action involves the modification of mitochondrial function and impaired energy metabolism that is a common characteristic and driver of the pathology.
Abstract 4135447: Demographics, Clinicopathological Outcomes and Comparative Survival Analysis of Pleural and Pericardial Mesothelioma; A Retrospective Population-Based Study
Authors: Rozi Khan, Agha Wali, Abdul Qahar Khan Yasinzai, Asif Iqbal, Amir Sohail, Aman Goyal, Kaleem Ullah, Bisma Tareen, Marjan Khan, Hafeez Ullah, Sayed Ab Reshad Ghafouri, Mary Elhawi, Ahmed Mahmood, Sethi Pooja, Asad Ullah
Journal: Circulation (2024)

Background: Malignant mesothelioma (MM) is an aggressive and rare tumor of mesothelial cells that is strongly correlated with asbestos exposure. Due to its long latency period, MM is characterized by its poor prognosis. In this study, we primarily analyzed data for the clinicopathological analysis of malignant pleural mesothelioma with comparative overall survival (OS) and cancer-specific survival (CSS) with primary pericardial mesothelioma. Method: The data was collected from the Epidemiology and End Results (SEER) database, comprising 12,991 mesothelioma patients from 2000 to 2020. Results: A total of 12,991 cases of MM were extracted from the database, of which 99.55% were pleural and only 0.177% were pericardial. The median age was 74 years. Regarding gender, 80% of the patients were male. MM was found to be more common in older age (&gt;65, 77%). 52% of the patients had a tumor size greater than 5 cm. The common histologic type was mesothelioma NOS (45%), followed by the epithelioid type (36%). The most common treatment modality was chemotherapy. Multivariate analysis showed better survival outcomes in younger, female patients undergoing combination therapies. Moreover, the histologic subtype, especially epithelioid mesothelioma, showed the overall best prognosis. Regarding comparative OS and CSS between pleural and pericardial mesothelioma, the 3-year OS of pleural mesothelioma was 11.2% (95% CI: 0.107 - 0.118) and for pericardial mesothelioma, the 3-year OS was 4.7% (95% CI: 0.007 - 0.317). Pleural mesothelioma had a 1-year CSS of 37.1% (95% CI: 0.343 - 0.401), and for pericardial mesothelioma, the CSS at 9 months was 28.6% (95% CI: 0.089 - 0.922), and all patients survived &lt; 1 year in the cohort. Conclusion: Malignant mesothelioma is a rare and aggressive tumor. Pericardial mesothelioma has lower survival in comparison to pleural mesothelioma. Genomic analysis and including all ethnicities in future clinical trials will help in future personalized therapeutic approaches.
Abstract 4136705: Complexity and Inconsistency of Echocardiogram Prices at Top-Rated Hospitals in the United States
Authors: Austin Triana, R. Van Horn, Mason Alford, Joseph Quintana, R. Van Horn
Journal: Circulation (2024)

Background: Recent U.S. policies require hospitals and health insurers to post payer-specific negotiated prices for services. Few studies, if any, have thoroughly investigated the accuracy of these payer-specific prices for individual hospitals. Hypothesis: Top-rated medical centers charge consistent prices for echocardiograms, which are reflected in price transparency files. Aim: To evaluate the concordance of prices of echocardiograms using three datasets: 1) hospital price transparency, 2) payer price transparency data, and 3) Electronic Remittance Advice (ERA) claims data, reflecting actual payments. Methods: We extracted prices for transthoracic echocardiograms (CPT 93306) at 22 top-rated hospitals by US News&amp;World Report from 1/1/2022 to 12/31/2022. We used price transparency data aggregated by Turquoise Health and compared with ERA claims data. This analysis included 9,171 insurance claims, matched to either payer or hospital-reported prices. For each claim, concordance between datasets was determined by evaluating whether each claim payment fell within a $10 margin of a publicly reported payer-specific price. Findings: In the payer and hospital price transparency files, reported prices ranged from $1.3 to $34,424. In the ERA claims data, the median payment for the professional fee was $203 (Q1 = $116, Q3 = $245), and the median payment for the facility fee was $2682 (Q1 = 1829, Q3 = $4531). There was a ten-fold difference in median price between the cheapest and most expensive facility. Only 27.4% of claim payments had a concordant price in the payer price transparency dataset, and 11.9% in the hospital dataset. Conclusion: Deriving accurate price estimates for patients requires precise matching of the insurance plan, place of service, and fee type. This process highlights the complexity of insurance contracting, and it is not surprising that there is some disagreement in prices. Regardless, we are hopeful that highlighting variation and complexity in prices is a step towards a better system of healthcare payments in the United States.
Abstract 4135741: Perioperative and Long-term Impact of Contemporary Optimal Guideline-Directed Medical Therapy in Patients with Reduced Ejection Fraction Undergoing Aortic Valve Surgery for Pure Severe Chronic Aortic Regurgitation
Authors: Alexandre Cinq-Mars, Marie-Christine Blais, Roxanne St-Louis, Charline-Hélyette PUJOS, Montse Massot, Jean-Benoît Veillette, Florence Bernier, Pierre Yves Turgeon, David Belzile, Mathieu Bernier, Francois Dagenais, Mario Senechal
Journal: Circulation (2024)

Background: Although recent studies have showed improved outcomes, aortic valve replacement (AVR) for chronic aortic regurgitation (AR) in the presence of reduced left ventricular ejection fraction (LVEF) is associated with a higher surgical risk. Contemporary long-term outcome remains poorly investigated. Methods: Between January 2004 and August 2019, we identified 122 patients who underwent AVR for pure chronic severe AR with LVEF less than 50%. Patients with severe reduced LVEF (&lt;35%, n=37) were compared with those with mild to moderate reduced LVEF (35% to 50%, n=85). Results: Preoperative and intraoperative characteristics were similar in both groups. Operative mortality for the entire cohort was 1,6% (n=2) and similar across the LVEF spectrum. Postoperative intra-aortic balloon pump has been used in 2/37 patients with LVEF &lt; 35% compared to 0/85 patients with LVEF 35-50% (p = 0.09). Patients with severely reduced LVEF had a longer length of stay (10.1±5.5 vs 7.8±3.5 days, p=0,02) while the rate of stroke, atrial fibrillation, acute renal failure, and pulmonary infection were similar between groups. Postoperatively, optimal medical therapy was achieved in most patients and more than a quarter of patients with LVEF &lt; 35% benefited from cardiac resynchronization therapy. At the latest follow-up, mean LVEF was 42±12% in the severe reduced LVEF (vs. baseline 28±6%, p&lt;0.001) and 51±9% in the mild to moderate reduced LVEF group (vs. baseline 45±4%, p&lt;0.001). Freedom from cardiovascular (CV) death at ten years was 87.2% in the severe reduced LVEF group and 94.7% in patients with mild to moderate reduced LVEF (p=0.10). Freedom from heart failure (HF) hospitalization at ten years was higher in the mild to moderate reduced LVEF group (96.3%) than in the severely reduced LVEF group (88.3%) (p=0.009). Conclusion: In this contemporary cohort of patients undergoing AVR for chronic severe AR, patients with severely reduced EF treated with optimal guideline-directed medical therapy had a similar operative mortality and freedom from CV death than patients with mild to moderate reduced LVEF. Favorable left ventricular remodeling was observed in both groups at 1 year follow-up. Hospitalization for HF was low with less than 15% in both groups at 10 years follow-up; although rehospitalisation occurred more frequently in severe reduced LVEF group.