tbuckley/cabot-search huggingface dataset:
Abstract 4144434: Cardiac Amyloidosis: Hidden in Plain Sight
Authors: Hera Jamal, Michael LaLoggia, Rachel Moshman, Maura Powell, Vivek Kulkarni
Journal: Circulation (2024)

Introduction: Cardiac amyloidosis (CA) is the most common cause of restrictive cardiomyopathy (CM). CA is most often due to deposition of transthyretin (ATTR-CM). ATTR-CM is prevalent in 10-14% of patients diagnosed with heart failure with preserved ejection fraction (EF &gt; 50%) (HFpEF). Despite clinical advancements and increased awareness, CA remains under-detected. Questions: Are patients admitted with HFpEF being adequately screened for CA? Will an educational intervention and implementation of an electronic order set for CA improve screening rates? Goals: Identify screening rates for CA, and improve comfort level recognizing and screening for CA at a tertiary care institution. Methods: A retrospective review was conducted of patients admitted to an academic tertiary care hospital in New Jersey from 1/1/22-6/30/22 with a diagnosis of HFpEF. Data collected included previous diagnosis of CA, presence and results of a technetium-99m pyrophosphate (PYP) scan, serum and urine tests for monoclonal proteins (including electrophoresis with immunofixation and free kappa/lambda light chains ratio). An educational intervention was then provided to internal medicine (IM) residents regarding CA pathophysiology and screening (topics detailed in Figure 1). Pre- and post-intervention surveys were administered. Results were analyzed for significance with a paired t-test. Results: Of 498 patients admitted with HFpEF, only 23 (4.6%) were screened for a diagnosis of CA. Of those screened, only 14 (60%) received all appropriate diagnostic testing. The most often omitted test was the PYP scan in 30% of patients. IM residents reported modest comfort with CA screening before the intervention and a significant improvement after the intervention (Figure 1). Conclusion: Screening for CA in patients admitted with HFpEF is limited. An educational intervention significantly improved resident comfort level regarding screening for CA. Based on these findings, an electronic order set was created for comprehensive screening of CA; post-intervention screening rates will be assessed in the future.
Abstract 4144446: Efficacy and Safety of Empagliflozin after Acute Myocardial Infarction: A Systematic Review and Meta Analysis
Authors: Zina Otmani, Mazen Negmeldin Aly Yassin, Hazem Ayman Elsayed, Farouq Alahmed, Bashar M. Al Zoubi, Omar Hany Mohammed, Abdelbassat Belakhdar, Ahmed K. Awad
Journal: Circulation (2024)

Introduction: Empagliflozin, a sodium–glucose co-transporter-2 (SGLT-2) inhibitor, improves cardiovascular outcomes in patients with heart failure (HF) with or without diabetes mellitus. However, limited data is available regarding its impact after acute myocardial infarction (AMI). Therefore, we aimed in our meta-analysis to evaluate the safety and efficacy of empagliflozin after AMI. Methods: We searched PubMed, Scopus, Cochrane Library, and Web of Science from inception to April 19th, 2024, to identify any Randomized Controlled trials (RCTs) that compare empagliflozin to placebo after AMI. The safety outcomes were presented as short term cardiovascular mortality, all-cause mortality, hospitalization for heart failure (HF), and any adverse events. The efficacy outcomes were reported as NT-proBNP, systolic blood pressure (SBP), diastolic blood pressure (DBP), and LDL-c. Dichotomous outcomes were pooled in the form of risk ratio (RR), and continuous outcomes in form of mean difference (MD), with the corresponding 95% confidence intervals (CI). Results: Ten RCTs with a total of 10,697 patients were included. Empagliflozin was associated with significant lower risk of cardiovascular mortality (RR = 0.57, 95% CI [0.46, 0.71]), all cause mortality, and hospitalization for heart failure, (RR=0.64, 95% CI [0.53, 0.79]), (RR = 0.67, 95% CI [0.58, 0.79]), respectively. Furthermore, empagliflozin demonstrated a significant reduction in both NT-proBNP (MD = -161.26, 95% CI [-294.58, -27.93]) and SBP (MD= -8.59, 95% CI [-13.26, -3.93]). However, there is no difference between the two groups in terms of any adverse events, diastolic blood pressure, and LDL-c, (RR=0.98, 95% CI [0.95, 1.02]), (MD = -2.55, 95% CI [-5.31,0.20]), (MD=1.67, 95% CI [-6.11, 9.46]), respectively. Conclusion: Our meta analysis reveals that empagliflozin significantly reduce all major cardiovascular outcomes after AMI such as cardiovascular mortality and hospitalization due to heart failure. Moreover, empagliflozin effectively lowers NT-proBNP levels and SBP with no superiority in terms of adverse events, diastolic blood pressure and LDL-c.
Abstract 4144749: Evolving Trends and Outcomes of P2Y12 Inhibitor Pretreatment in Non-ST-Elevation Acute Coronary Syndrome in the United States: Insights from the NCDR Chest Pain-MI Registry
Authors: Hiroki Ueyama, kevin kennedy, Jennifer Rymer, Alexander Sandhu, Toshiki Kuno, Frederick Masoudi, John Spertus, Shun Kohsaka
Journal: Circulation (2024)

Background: Although high rates of P2Y12 inhibitor pretreatment for non-ST-elevation acute coronary syndrome (NSTE-ACS) have been reported, contemporary practice pattern in the U.S. are not well studied. Objectives: To investigate the temporal trends, variability, and clinical outcomes of P2Y12 inhibitor pretreatment in NSTE-ACS across U.S. Methods: Consecutive patients that underwent early invasive strategy for NSTE-ACS (coronary angiogram ≤ 24 hours of arrival) in National Cardiovascular Data Registry (NCDR) Chest Pain-Myocardial Infarction (MI) registry was analyzed. Initially, a time-trend analysis was conducted on the complete cohort from January 1, 2013, to March 31, 2023. Subsequently, a more recent cohort (January 1, 2019, to March 31, 2023), with a complete set of variables, was used to construct a hierarchical regression model to quantify variability in the use of pretreatment among institutions and hospital regions. For this contemporary cohort, instrumental variable analysis was performed to compare in-hospital outcomes between patients who received pretreatment and those who did not. Results: Use of P2Y12 inhibitor pretreatment has decreased from 24.8% in 2013Q1 to 12.4% in 2023Q3. Among the contemporary cohort of 110,148 patients (2019-23; mean age, 63.9 [SD 12.5] years; 33.0% female), 17,509 (15.9%) received pretreatment. Significant variability in P2Y12 inhibitor pretreatment was observed (range: 0-100%): hierarchical regression model demonstrated that two identical patients would have more than a three-fold difference in the odds of pretreatment by changing institution or hospital region (OR 3.63; 95% CI, 3.51-3.74 and 3.21; 95% CI, 2.90-3.54, respectively). Instrumental variable analysis demonstrated no significant differences in in-hospital all-cause death (1.5% vs 1.7%; p=0.071), recurrent MI (0.56% vs 0.57%; p=0.98), or major bleeding (2.7% vs 2.8%; p=0.98) between the two groups. However, in patients who underwent coronary artery bypass surgery, pretreatment was associated with a longer length of stay (11.2 ± 5.1 days vs 9.8 ± 5.0 days; p &lt; 0.001). Conclusions: Within the nationwide registry in the U.S., we observed a significant variability in the use of P2Y12 inhibitor pretreatment among NSTE-ACS patients in the U.S. Given the lack of clear advantages and the potential for prolonged hospital stays, our findings highlight the importance of efforts to improve standardization.
Abstract 4144768: Hypogenesis of Lymphatic Vessels in the Mitral Valve of Fibrillin-1 Mutant Mouse
Authors: CAN TAN, Stephen Chiu, Tsutomu Kume
Journal: Circulation (2024)

Marfan Syndrome (MFS) is an autosomal-dominant cardiovascular disorder usually associated with the heterozygous mutation in the FBN1 gene, which encodes fibrillin-1, a structural macromolecule that polymerizes into microfibrils in connective tissue. Fibrillin-1 regulates the bioavailability of transforming growth factor (TGF) β1, a vital cytokine that modulates various cell activities. Enhanced TGFβ signaling induced by Fbn1 mutation is a major contributor to the MFS pathogenesis, one of which is myxomatous mitral valve degeneration that can cause mitral valve prolapse, with an incidence of about 45% in FBN1 mutant individuals. There is evidence that fibrillin microfibrils are present in the wall of lymphatic vessels, and that increased expression of TGFβ1 can inhibit lymphatic endothelial cell (LEC) proliferation during wound repair in mouse tail skin. We recently demonstrated the distribution and function of lymphatic vessels in murine mitral valves. However, the effects of FBN1 mutation on the formation and maintenance of lymphatic vessels in mitral valves have yet to be elucidated. To investigate the distribution and structure of lymphatic vessels in mitral valves of Fbn1 mutant mice, whole-mount immunostaining labeled with the LEC marker VEGFR3, as well as the endothelial markers CD31 and VE-cadherin, was performed on the mitral valves of adult (6-week-old) Fbn1 heterozygous mutant mice and their WT littermates. We found that the density of lymphatic vessels and the number of lymphatic branching points in mitral valve leaflets in Fbn1 heterozygous mutant mice were decreased, accompanied by the discontinued cell-cell junctions in capillary LECs, as compared to the WT littermates. Further investigation revealed that lymphatic vessels were formed in the WT mitral annulus at postnatal day 7 (P7) but not embryonic day 18.5 (E18.5). In contrast, no lymphatic vessels were found in the Fbn1 mutant mitral annulus at P7. These results suggest that the increased TGFβ signaling pathway due to the Fbn1 mutation leads to hypoplasia of lymphatic vessels in the mouse mitral valve, which may affect the lymphatic function and therefore be a cause of the mitral valve prolapse. Further studies are underway to determine the lymphatic functions in Fbn1 mutant mitral valve as well as to analyze the lymphatic vessels in human myxomatous degenerated mitral valve samples.
Abstract 4144440: Where We Work Correlates with Whether We Receive Cardiorespiratory Preventive Care Services
Authors: Wan-Chin Kuo, Bridget Lally, Dian Luo, Roger Brown
Journal: Circulation (2024)

Background: More than 20% of Americans do not regularly receive cholesterol screening and flu shots, the two important preventive services for cardiorespiratory self-care. Uncontrolled dyslipidemia leads to cardiovascular diseases (CVD), the leading cause of death and disability among American workers, while influenza contributes to health-related workplace absenteeism. Despite the loss of productivity in workers due to cardiorespiratory illness, only a few studies examined occupational disparities in cardiorespiratory preventive care services. This study aimed to examine the association between occupational characteristics and the utilization of cholesterol screening and flu shots. Methods: The Health and Retirement Study (HRS) is a longitudinal survey of middle-aged and older adults in the U.S. This study focused on 3,222 participants in the HRS from 2004 to 2018, representing the past and current working population. Respondents who did not report cholesterol screening, influenza vaccination, or job information, passed away by 2019, never worked for pay, or had CVD/stroke were excluded from the analysis. Occupation was coded based on the U.S. Census 2000 and configured into five groups: (1) management/science, (2) social services, (3) general services, (4) health services, and (5) industrial workers. Job characteristics, including psychological and physical strains at work, ergonomic risk, lifting of heavy loads, and job stability, were based on self-reported questions. The multivariable logistic and ordered logistic regression models were used for analysis. Results: Compared to the management/science workers, industrial and general services workers were less likely to have optimal cholesterol screening and influenza vaccination. For cholesterol screening behaviors, frequent heavy lifting at work (p=0.010), lower job mental strain (p=0.004), and lower job stability (p=0.025) were associated with a lower likelihood of optimal cholesterol screening, after the adjustment for demographic and health covariates. For flu-shot intake, higher job physical strain (p&lt;0.001) and lower job stability (p=0.002) were associated with a lower likelihood of optimal influenza vaccination. Conclusion: Findings highlight the underutilization of cholesterol screening and flu shots among industrial workers and general services workers. Multi-level stakeholder engagement is warranted to gauge the return on investment and sustainability of preventive health programs at workplaces.
Abstract 4144372: TET2-mutant Clonal Hematopoiesis Promotes Heart Failure with Preserved Ejection Fraction
Authors: Ambarish Pandey, Toby Thomas, yuanyuan ji, Benjamin Kroger, Camila Irion, Fatma Kalkan, Matthew Segar, Vinayak Subramanian, Antoni Bayes-Genis, Wenhuo Hu, Albert Son, Kira Young, Jennifer Trowbridge, Peter Carlsgaard, Naveen Premnath, nan jiang, Daniel Daou, Sarah Ware, Stephen Chung, Dan Tong
Journal: Circulation (2024)

Introduction: Aging and inflammation are both important risk factors of heart failure with preserved ejection fraction (HFpEF). However, a potential mechanistic link between them in HFpEF pathogenesis remains unknown. Clonal hematopoiesis of indeterminate potential (CHIP) is a common age-related condition characterized by the clonal expansion of hematopoietic stem cell (HSCs) bearing mutations in certain driver genes and is associated with increased inflammation and elevated risk of cardiovascular diseases. However, our understanding of the role of CHIP in HFpEF remains limited. Methods and Results: We evaluated the prevalence and clinical impact of CHIP in two independent and well-annotated HFpEF cohorts. We compared a single-center registry of deeply phenotyped HFpEF cases at UT Southwestern with age- and sex-matched controls from the Dallas Heart Study (N=108 each), observing that the prevalence of CHIP was significantly higher in HFpEF patients as compared to matched controls (25% vs 19%). We also discovered that TET2 is the most frequently mutated gene in this population (63% in HFpEF vs 40% in controls), while DNMT3A mutations were underrepresented (30% vs 45%). We validated these findings in an external cohort of HFpEF patients from the TOPCAT trial (N=213). Importantly, we discovered that the presence of CHIP is independently associated increased risk of heart failure hospitalization and all-cause mortality (adjusted HR 2.07, 95% CI: 1.01-4.22, p = 0.046). To determine whether CHIP causally links with HFpEF, mice received Tet2 knockout (KO) vs wildtype bone marrow, and were subjected to a well-established “two-hit” HFpEF induction model. Despite similar systemic responses, the Tet2 KO group manifested exacerbated diastolic dysfunction. This effect is Tet2 specific, as mice harboring HSCs loss of Dnmt3a did not develop such phenotype. Bulk and single-cell RNASeq analyses revealed that HFpEF induction led to an expansion of pro-inflammatory and pro-fibrotic macrophage subsets in the heart, which was exacerbated by CHIP. There is an enrichment of NLRP3/ IL1b inflammatory genes in the Tet2 KO group, and NLRP3 deficiency in HSCs attenuates the phenotype of Tet2 KO-associated HFpEF. Conclusion: Our results reveal that TET2-mediated CHIP is highly prevalent in HFpEF patients and directly promotes HFpEF pathogenesis. CHIP status could serve as a marker for risk stratification and targeted anti-inflammatory therapies in patients with HFpEF.
Abstract 4144695: Comparative cardiovascular efficacy of empagliflozin and dapagliflozin in patients with type 2 diabetes: A systematic review and meta-analysis
Authors: Muhammad Ammar Samad, Eman Mahboob, Mushood Ahmed, Sabeeh Farooqui, Shaikh Tahir Ali, Shanzay Akhtar, Adeel Ahmad, Asad Rahman, Hritvik Jain, Raheel Ahmed
Journal: Circulation (2024)

Background: The favorable safety profile of sodium-glucose cotransporter 2 (SGLT2) inhibitors, notably empagliflozin and dapagliflozin, make them a suitable treatment option for type 2 diabetes mellitus (T2DM). However, their comparative efficacy and cardiovascular (CV) benefits still remain unclear. This meta-analysis aims to compare the CV outcomes between Dapagliflozin and Empagliflozin in T2DM patients, exploring their varying effectiveness. Methods: A comprehensive search of electronic databases, PubMed, Embase, and Google Scholar was conducted from inception till May 2024. The study was conducted adhering to the PRISMA guidelines. Following a thorough screening and quality assessment, primary outcomes including major adverse cardiovascular events (MACE), cardiovascular (CV) mortality, and all-cause death along with secondary outcomes including stroke, myocardial infarction (MI), and heart failure (HF), were extracted. The random effects model was used to pool the odds ratio (OR) along with the corresponding 95% confidence intervals (CIs) for all outcomes. A p-value of less than 0.05 was considered statistically significant. Results: We pooled 6 studies with a total of 172,293 participants. The evaluation of pool results showed a significant association between the use of empagliflozin and dapagliflozin for reducing CV mortality (OR 1.15, 95 % CI 1.01- 1.30; p=0.04) and MACE (OR 1.15, 95 % CI 1.01- 1.30; p=0.04). However, we found no statistically significant difference between the two drugs for reducing MI (OR 1.04, 95 % CI 0.90- 1.19; p=0.59), Stroke (OR 0.92, 95 % CI 0.76- 1.11; p=0.40), HF (OR 1.30, 95 % CI 0.93- 1.81; p=0.13) and all-cause death (OR 1.33, 95 % CI 0.46- 3.88; p=0.60). After running the sensitivity analysis, a statistically significant result was observed between use of empagliflozin and dapagliflozin for HF (OR 1.47, 95 % CI 1.13- 1.90; p=0.004). Conclusion: The use of dapagliflozin significantly reduces CV mortality and MACE when compared with empagliflozin. However, the incidence of MI, stroke, HF, and all-cause death is comparable across the two groups. Our results should be considered hypothesis generating and evidence from large-scale multi-centric randomized controlled trials (RCTs) is required to reach a definitive conclusion
Abstract 4144740: Characteristics and Natural History of Early ATTR Cardiac Amyloid Infiltration
Authors: Aldostefano Porcari, Yousuf Razvi, Francesco Cappelli, Christian Nitsche, Matteo Serenelli, Simone Longhi, Giulio Sinigiani, Alberto Cipriani, Alberto Aimo, Valentina Allegro, Daniela Tomasoni, Mattia zampieri, Anna Cantone, Ahmad Masri, Marcus Urey, Adam Ioannou, Aviva Petrie, Finn Gustafsson, Carol Whelan, Michele Emdin, Marco Metra, Gianfranco sinagra, Helen Lachmann, Ashutosh Wechalekar, Philip Hawkins, Julian Gillmore, Marianna Fontana
Journal: Circulation (2024)

Background: Patients with transthyretin (ATTR) cardiac amyloid infiltration are increasingly diagnosed at earlier disease stages with no heart failure (HF) symptoms and a wide range of cardiac amyloid infiltration. Aim: The aim of the study was to characterize the natural history and long-term outcomes of patients with ATTR cardiac amyloid infiltration and no HF symptoms. Methods: Data of consecutive patients at 12 international centres for amyloidosis (2008-2023) were analysed. Asymptomatic ATTR cardiac amyloid infiltration was defined as absence of HF and diuretic therapy, monoclonal gammopathy with evidence of cardiac uptake on bone scintigraphy (Perugini grade 1 to 3). Results: The study comprised 660 patients with ATTR cardiac amyloid infiltration and no HF symptoms (74.1±9.7 years, 87% male, 21.5% hereditary ATTR amyloidosis), 81.5% (n=538) with Perugini grade 2 and 3, and 18.5% (n=122) with Perugini grade 1. The number of new diagnoses progressively increased over time, from 27 in 2008-2011 to 350 in 2020-2023. Perugini 2 and 3 patients exhibited significant cardiac functional and structural abnormalities, in keeping with ATTR cardiomyopathy, whilst Perugini grade 1 patients generally had normal cardiac structure and function. At 3 years, the rate of cardiovascular (CV) events in the overall population was elevated and consistently higher in Perugini grade 2 and 3 compared to grade 1 (development of symptomatic HF [50% vs 23%], diuretic initiation and NT-proBNP progression [32.5% vs 12.6%], HF hospitalization [6.6% vs 0%] and unplanned CV hospitalization [16.7% vs 4%]) (Figure 1). Over 38 months (IQR 22-61), the death rate was high, and similar in Perugini grade 1 vs 2 and 3 (5.0 vs 4.5 deaths per 100 patient-years), however Perugini grade 2 and 3 patients had a 3-fold higher risk of CV mortality (hazard ratio [HR] 3.0 [95%CI 1.19-7.56], p=0.020) compared to Perugini grade 1 (Figure 2). Conclusions: Asymptomatic ATTR cardiac amyloid infiltration is increasingly common and encompasses a wide spectrum of disease severity. The Perugini grade enables potential characterization of patients into clinical profiles with varying disease progression and risks of CV and non-CV mortality. In the absence of randomized trials, these data may inform clinicians regarding the use of disease-modifying treatment in patients with asymptomatic ATTR cardiac amyloid infiltration.
Abstract 4144673: 1-Year Outcomes After Cardioversion With and Without Anticoagulation in Patients With Left Atrial Appendage Occlusion: A Propensity-Matched Analysis
Authors: Sittinun Thangjui, Angkawipa Trongtorsak, Jakrin Kewcharoen, Harshith Thyagaturu, HangYu Watson, Samuel Mensah, sudarshan balla, Leenhapong Navaravong
Journal: Circulation (2024)

Background: Left atrial appendage occlusion (LAAO) is an alternative primary stroke prevention strategy for patients with atrial fibrillation (AF) who cannot tolerate anticoagulation (AC). Following LAAO implantation, patients typically undergo testing after 45 days to confirm successful occlusion and potentially discontinue AC. Some patients with LAAO may require cardioversion (CVN) due to recurrent AF. However, data is limited on whether post-CVN management in these patients should mirror that of patients without LAAO. Therefore, we report the outcomes of patients with LAAO who underwent CVN and were empirically treated with or without AC post-CVN. Methods: Using the TriNetX database, we identified patients aged ≥ 18 years who had LAAO, underwent CVN, and were not on AC prior to the procedure. Patients were included if they received AC for at least 4 weeks after CVN (AC group) or did not receive AC (Non-AC group). Propensity score matching was performed to adjust for confounders between the two groups. Thromboembolic and bleeding outcomes were assessed at 1 year post-CVN. Results: Among 1,086 patients, 84 (7.7%) received anticoagulation after CVN. After propensity score matching, 158 patients (79 in each group) were included, with a mean age of 71.8 ± 11.3 years (49% female) in the AC group and 70.6 ± 12.5 years (39% female) in the Non-AC group. At 1 year, the incidence of composite thromboembolic events was similar between the AC and Non-AC groups (12.7% vs. 12.7%; OR = 1.00, 95% CI: 0.39-2.55). Most thromboembolic events occurred within 2 weeks post-CVN. There were no significant differences in the composite outcomes of intracranial bleeding, gastrointestinal bleeding, or need for blood transfusion between the AC and Non-AC groups at 1 year (OR = 0.86, 95% CI: 0.30-2.25). Conclusion: Data suggest that most patients with LAAO do not receive AC after CVN. Additionally, the use of anticoagulation post-CVN in patients with LAAO did not statistically reduce thromboembolic events nor increase bleeding risk.