tbuckley/cabot-search huggingface dataset:
Abstract 11748: A Retrospective Observational Study Exploring Real-World Diagnostic Workup of Patients With Wild-Type Transthyretin Amyloid Cardiomyopathy and/or Light Chain Amyloidosis
Authors: Cindi Sounthonevat, Jose Alvir, Patrick Feron, Aaron Crowley, Darrin Benjumea, Yong Chen, Haechung Chung
Journal: Circulation (2023)

Introduction: Light chain (AL) and transthyretin amyloidosis are the most common forms of cardiac amyloidosis. Despite having similar presentation, the prognosis and treatment pathways are distinct, placing importance on accurate diagnosis. Aim: Assess the real-world diagnostic workup for AL in patients with AL, wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM), or both (AL+ATTRwt-CM). Methods: A retrospective study of Optum EHRs from Jan 2019-Dec 2021. Diagnostic workups in the 24 months prior to first diagnosis (index date) were assessed in mutually exclusive patient cohorts (aged ≥18 years) with AL (ICD10: E85.81 not E85.82), ATTRwt-CM (ICD10: E85.82 not E85.81), or AL+ATTRwt-CM (both ICD10 codes). Results: Of 49,466,996 patients in the database, 996, 526, and 31 met criteria for the AL, ATTRwt-CM, and AL+ATTRwt-CM cohorts, respectively ( Table ). Notable proportions of patients had no relevant workups (40%, 24%, and 23%) or no AL workups (40%, 29%, and 23%). Across cohorts, 54% (AL), 35% (ATTRwt-CM), and 61% (AL+ATTRwt-CM) received a workup for AL only, and &gt;60% had 1-3 types of AL workup. Among patients tested with the serum-free AL assay (n=681), serum (n=460), or urine (n=286) immunofixation (IF) methods, ≥60% were in the AL cohort; ≤36% were in the ATTRwt-CM cohort and ≤4% in the AL+ATTRwt-CM cohort ( Figure ). Conclusions: In Optum EHRs, &gt;20% of patients diagnosed with ATTRwt-CM or AL+ATTRwt-CM, and 40% with AL, had no relevant workups. Due to clinical urgency, it is critical to rule out AL in patients with cardiac amyloidosis using the AL assay or IF. These findings highlight the need for better diagnostic pathways for patients with suspected AL or ATTRwt-CM.
Abstract 11705: Events of Device Failure in Elderly Patients Undergoing Watchman Device Insertion in the United States
Authors: Jasninder Dhaliwal, Rahat A Memon, Shruti Aggarwal, Kamleshun Ramphul, Shaheen Sombans, Hemamalini Sakthivel
Journal: Circulation (2023)

Introduction: Watchman device implant reduces various cardio-cerebral events in patients with left atrial appendage. As there is a lack of data on device failure among the elderly undergoing this procedure, we aim to provide a perspective via the 2016-2020 National Inpatient Sample(NIS). Methods: Watchman procedures in patients ages ≥60 years, with a history of atrial fibrillation or flutter, were examined for our study from the NIS. Events of device failure were considered, and variables that may influence such events were studied via logistic regression models. Results: We found 85190 procedures for Watchman device insertion conducted in the United States, and 510 (0.6%) cases reported an event of device failure. Procedures at rural centers reported higher odds of device failure than urban teaching centers (1.3% of rural center procedures vs. 0.6% of urban teaching hospital procedures, aOR 2.970, 95% CI 1.965 -4.488, p&lt;0.01). Meanwhile, patients with a history of CKD (aOR 0.565, p&lt;0.01), hypertension (aOR 0.500, p&lt;0.01), and peripheral vascular diseases (aOR 0.513, p=0.012) showed reduced odds. Several complications were also noted among those with device failure, as 20 cases (3.9% ) had acute kidney injury, 45 patients (8.8%) developed cardiac tamponade, 70 cases (13.7%) had pericardial effusion, and 20 cases (3.9%) necessitated mechanical ventilation. The mean CHA 2 DS 2 -VASc score among patients with device failure was 4.65 (vs. 4.68, p=0.029), and the mean Charlson Comorbidity Index score was 1.42 (vs 1.65, p&lt;0.01). Patients with device failure had a more expensive stay (mean hospital charge $144936 vs. $122504). Conclusions: Device failure was a rare but severe complication involving 0.6% of procedures in our analysis. Many comorbidities influenced events of device failure. As our study found a higher incidence among procedures done in rural centers, further studies to screen and assess the patients and monitor their condition may help improve the outcomes.
Abstract 11723: Predictors of Post-Operative Atrial Fibrillation in Patients Undergoing Stress Echocardiography Prior to Noncardiac Surgery
Authors: Kevin M Stanko, Toby Weingarten, Garvan Kane, Robert B McCully, Patricia A Pellikka, Karen Mauck, Michael W Cullen
Journal: Circulation (2023)

Background: Atrial fibrillation (a-fib) occurs in up to 40% of patients after noncardiac surgery and is associated with increased risk of adverse outcomes. Practice guidelines recommend stress testing, including stress echocardiography (SE) to assess for coronary artery disease in selected high-risk patients prior to noncardiac surgery. The utility of using SE findings for predicting postoperative a-fib is unknown. Hypothesis: Myocardial ischemia can contribute to arrhythmogenic potential; other echocardiographic variables are likely associated with a-fib. Findings on SE may identify patients at risk for a-fib after noncardiac surgery. Aims: To determine if certain SE findings predict a-fib following noncardiac surgery. Methods: The study included patients undergoing pharmacological and exercise SE before noncardiac surgery. The primary outcome was a-fib/flutter within 30 days after surgery. Multivariate analysis was adjusted for age, cardiovascular comorbidities, and markers of surgical risk. Results: This analysis included 2,376 patients (mean age 68 +/- 7 years; 60% male); 1,986 patients had no known history of a-fib/flutter. Of these, 48 (2.4%) developed postoperative a-fib/flutter. In multivariate analysis, SE variables associated with development of new a-fib/flutter included left ventricular dilation (OR 2.11, p=0.049), increased left atrial volume (OR 1.19, p=0.045), and increased left ventricular mass index (OR 1.13, p=0.043) on rest images. The presence of ischemia or infarct on stress echocardiogram was not associated with postoperative a-fib/flutter. A total of 390 patients had a history of paroxysmal a-fib/flutter and were in sinus rhythm at the time of surgery. Of these, 90 (23%) experienced recurrent a-fib/flutter within 30 days of surgery. Multivariate analysis did not reveal any SE variables significantly associated with recurrence, including presence of myocardial ischemia or infarct at the time of SE. Conclusions: All SE variables associated with postoperative a-fib following noncardiac surgery are available from resting images alone. Therefore, SE that includes comprehensive resting images may offer benefit in the pre-operative evaluation of selected patients.
Abstract 11641: The Role of Inflammation in a Humanized Mouse Model of Transthyretin Cardiac Amyloidosis
Authors: Xiaokang Wu, Nixuan Cai, Alessandro Evangelisti, Alokkumar Jha, Y Joe Woo, Ronglih Liao, Kevin M Alexander
Journal: Circulation (2023)

Transthyretin cardiac amyloidosis (ATTR) is an under-diagnosed, progressive form of cardiomyopathy, leading to heart failure and death. It is caused by the deposition of amyloid fibrils in the myocardium derived from the plasma protein transthyretin (TTR), but its pathogenesis is poorly understood. Informative in vivo models have proven elusive. Our research identifies inflammation as a potential exacerbating factor in ATTR, suggested by gene expression elevations in inflammatory markers from cardiac biopsies of ATTR-CM patients. To explore this, we created a murine TTR knockout model expressing the human V122I TTR variant. Significant elevations of human TTR were observed in the plasma post-injection (human TTR level (ng/ml) ATTR: 110 ± 10; Control: 28 ± 12; p=0.0008, N=3-5) with preserved cardiac function (FS% ATTR: 20 ± 6; Control: 23± 5; p=0.8162, N=3-5). Notably, the mouse model exhibited amyloid deposits in the heart, confirmed by immunofluorescence and Congo Red staining. Transmission electron microscopy revealed both immature and mature amyloid fibrils in the extracellular matrix (Figure1). RNA-sequencing of the ATTR mouse heart identified distinct transcriptomic patterns and conserved inflammation pathways similar to those seen in a cohort of human ATTR heart samples, such as TNF, T-cell, and B-cell receptor signaling. Up-regulation of inflammatory markers, including CXCL1/2/3 and CCL20, was also observed, and an increased level of CCL5 (MFI ATTR: 801 ± 105; Control: 426± 64; p=0.0061, N=3) was confirmed via luminance-based immunoassay. These chemokines are critical for directing leukocytes to inflammation sites. This study suggests that inflammation may play a role in ATTR pathogenesis. Further in vivo studies are needed to elucidate the mechanisms by which inflammation modulates ATTR amyloidosis.
Abstract 11700: Left Ventricular Global Longitudinal Strain After Transcatheter Aortic Valve Implantation in Patients With Preserved Ejection Fraction
Authors: yuki matsubara, Michiyo Yamano, Tetsuhiro Yamano, Kan Zen, Satoaki Matoba
Journal: Circulation (2023)

Background: Left ventricular (LV) global longitudinal strain (GLS), which could assess subtle LV dysfunction, is already deteriorated in a certain number of aortic stenosis (AS) patients with preserved ejection fraction (EF). Although GLS improves after valve replacement, detailed outcome is not well understood. Research Question: In AS patients with preserved EF undergoing transcatheter aortic valve implantation (TAVI), is there a difference in post-procedural GLS between patients with and without reduced pre-procedural GLS? Aim: To elucidate the post-procedural course of GLS after TAVI. Methods: The present study was a single-center retrospective cohort study that included 119 out of 347 consecutive patients undergoing TAVI by excluding EF &lt;50%, atrial fibrillation, inadequate echo image for analysis, and loss to follow-up echocardiography. Subjects were divided into two groups according to pre-procedural GLS: reduced GLS (r-GLS) (&gt; -15%) and preserved GLS (p-GLS) (≤ -15%), and echocardiographic parameters at baseline and changes from baseline to mid-term follow-up (6 months to 1 year) were compared. Results: There was no significant difference in baseline characteristics ( Table ). Before the procedure, higher severity of AS, higher LV mass index and E/e’, and lower EF and peak left atrial longitudinal strain were observed in r-GLS. Both EF and LV mass index improved after TAVI in r-GLS and became comparable in p-GLS ( Figure ). After TAVI, GLS improved in r-GLS, but remained significantly inferior to p-GLS (-14.7 ± 2.3% vs. -16.5 ± 2.8%, P &lt; 0.001; Figure ). Conclusions: In AS patients with preserved EF, GLS improved after TAVI in patients with r-GLS but remained inferior to those with p-GLS, suggesting underlying refractory myocardial damage presumably caused by more severe AS and consequently more severe LV hypertrophy in patients with r-GLS. It might indicate the possibility of GLS for determining optimal timing of TAVI in AS patients with preserved EF.
Abstract 12133: Real-World Adherence to Mavacamten in Patients With Obstructive Hypertrophic Cardiomyopathy in the United States
Authors: Ahmad Masri, Ervant J Maksabedian Hernandez, Yan Wang, Weihua Gao, Aozhou Wu, Xu Han
Journal: Circulation (2023)

Background: There are no data on adherence to mavacamten in the real world. The first month of mavacamten treatment could be provided by the manufacturer for free before the drug is dispensed from commercial specialty pharmacies. Research Question: What is the adherence to mavacamten in patients with obstructive hypertrophic cardiomyopathy (HCM) in the real world? Aims: To assess the adherence to mavacamten in real-world patients with obstructive HCM. Methods: This was a retrospective cohort study of adult patients using the Symphony Integrated Dataverse that captured dispensing of commercial specialty pharmacies. Patients were included if they had ≥1 approved claim for mavacamten (the date of the first claim was the index date) from 4/28/2022 - 4/4/2023 and had continuous claims activity during the 12 months (baseline) before the index date. Discontinuation (defined as a gap ≥ 95 days in mavacamten treatment) and adherence (measured as proportion of days covered [PDC], modified medication possession ratio [MPRm], and compliance ratio [CR]) were evaluated during the follow-up that ended with the end of continuous claims activity or the end of the database, whichever was earlier. The use of background therapy was described at index. Subgroup analyses were conducted in patients with ≥2 approved mavacamten claims. Results: A total of 659 patients (mean ± SD age 64.2 ± 13.1 years, 63.0% female) were included ( Table ). During an average of 118 ± 76 days follow-up, 4.1% of patients discontinued mavacamten who were on treatment for an average of 56 ± 44 days. The PDC (mean ± SD) was 95.6 ± 7.1%, with 94.7% of patients having a PDC ≥ 80%. Overall, 22.8% of patients received mavacamten as a monotherapy without any background therapies at index. The subgroup analysis showed similar results and a MPRm (mean ± SD) of 99.5 ± 11.8%. Conclusion(s): Adherence to mavacamten over a mean of 118 days in the real world was high. Further follow-up is undergoing to understand adherence in a longer term.
Abstract 11758: Right Atrial Dysfunction is Associated With Atrial Arrhythmias in Adults With Repaired Tetralogy of Fallot
Authors: Omar Abozied, Ahmed Younis, Sriharsha Kandlakunta, Marwan Ahmed, Snigdha Karnakoti, Alexander C Egbe
Journal: Circulation (2023)

Introduction: Adults with repaired tetralogy of Fallot (TOF) have right atrial (RA) remodeling and dysfunction, and RA function can be measured using speckle-tracking echocardiography. There is limited data about the role of RA strain imaging in risk stratification in this population. Hypothesis: We hypothesized that RA reservoir strain could identify TOF patients at risk of developing atrial arrhythmia. We assessed the relationship between RA reservoir strain and atrial arrhythmias in adults with repaired TOF to test this hypothesis. Methods: Retrospective cohort study of adults with repaired TOF, and no prior history of atrial arrhythmias. Atrial arrhythmia was defined as atrial fibrillation, atrial flutter/atrial tachycardia, and categorized as new onset versus recurrent atrial arrhythmias. Results: We identified 426 patients (age 33±12 years; males 208 (49%)) that met the inclusion criteria. The mean RA reservoir, conduit, and booster strains were 34±11%, 20±9%, and 15±12%, respectively. Of 426 patients, 73 (17%) developed new-onset atrial arrhythmias (atrial flutter/tachycardia n=42; atrial fibrillation n=31); annual incidence 1.9%. RA reservoir strain was associated with new-onset atrial arrhythmias (adjusted HR 0.95, 95% CI 0.93-0.97) after multivariable adjustment. Of 73 patients with new-onset atrial arrhythmia, 41 (56%) had recurrent atrial arrhythmia (atrial flutter/tachycardia n=18; atrial fibrillation n=23); annual incidence 11.2%. Similarly, RA reservoir strain was associated with recurrent atrial arrhythmias (adjusted HR 0.92, 95% CI 0.88-0.96) after multivariable adjustment. Conclusions: RA strain indices can identify patients at risk for atrial arrhythmias, and this can, in turn, be used to guide the type/intensity of therapy in such patients.
Abstract 12125: Distribution of Myocardial Fibrosis in Patients With Non-Ischemic Cardiomyopathy and Ventricular Tachycardia Based on Genetic Variant
Authors: Nicholas Weinand, Kanae Hasegawa, Tiffany Hu, Travis Richardson
Journal: Circulation (2023)

Introduction: Patients with non-ischemic cardiomyopathy (NICM) have an increased propensity to develop arrythmias such as ventricular tachycardia (VT). A significant subset of patients with NICM have an underlying inherited genetic component. Hypothesis: This study evaluated the location of substrate for ventricular tachycardia in patients with NICM with proven genetic variants. We sought to characterize patterns of substrate location based on specific genetic variants. Methods: Patients referred for VT ablation between October 2018 and November 2022 at a single medical center were evaluated for pathologic genetic variants of known cardiomyopathy-related genes. Electro-anatomic mapping was reviewed for substrate localization. Results: Thirty-two patients with pathologic variants were evaluated (age 55 +/- 16 years, 94% male, left ventricular ejection fraction 34 +/- 13%). Mutations in TTN (n=11 of 32), LMNA (n=6 of 32), PKP2 (n=5 of 32), MYBPC3 (n=3 of 32), DSP (n=2 of 32), TTR (n=1 of 32), FNLC (n=1 of 32), AGL (n=1 of 32), DES (n=1 of 32), DSG2 (n=1 of 32), were observed. Mutations in TTN were associated with substrate in the basal periaortic region (100%) and basal septum (50%) (Figure 1). LMNA mutations were associated with mid inferolateral (60%) and apical inferolateral (60%) substrate. Substrate location for individuals with mutations associated with PKP2 were solely observed in the right ventricle. Conclusion: Certain genetic variants are associated with reproducible patterns of fibrosis in NICM. Understanding expected patterns of fibrosis based on genetic variants in NICM may facilitate ablation planning.
Abstract 12091: Actual Management of Venous Thromboembolism Complicated by Antiphospholipid Antibody Syndrome in Japan. From the Command VTE Registry-2
Authors: Takahiro Kuno, Norimichi Koitabashi, Yoshiaki Ohyama, Noriaki Takama, Ryuki Chatani, kazuhisa kaneda, Yuji Nishimoto, Nobutaka Ikeda, Yohei Kobayashi, Yugo Yamashita, Hideki Ishii
Journal: Circulation (2023)

Background: Venous thromboembolism (VTE) complicated with antiphospholipid antibody syndrome (APS) requires long-term anticoagulation to prevent the recurrent thrombosis. Direct oral anticoagulants (DOACs) have been widely used for VTE, but the guideline recommendations for their use are less favorable for APS-complicated VTE. There are no reports on the actual practice of APS complicated VTE in Japan in the DOAC era. So we investigated the actual practice and prognosis in APS-associated VTE, particulary with regard to the use of DOACs. Methods: COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. In this cohort, we examined the differences in actual VTE practice between patients with and without APS. Results: The current study population consisted of 83 APS-complicated VTE (mean age, 55; 53 male patients [63.9%]), and 5,114 VTE patients without APS (mean age, 68; 3010 male patients [58.9%]). Compared with patients without (w/o) APS, those with (w/) APS were more likely to have proximal deep vein thrombosis (DVT) than distal DVT, but the rate of pulmonary embolism was comparable. There was no difference in the rate DOAC use between patients w/[74.7%] and w/oAPS [79.5%]. All-cause mortality was significantly lower in the APS group (w/APS 6 [7.2%]; w/oAPS 1317 [25.8%]), VTE recurrence rates were similar (w/APS 8 [9.6%]; w/oAPS 275 [5.4%]), and the interval to VTE recurrence was significantly longer in the APS group (median: w/APS, 1050 days; w/oAPS 724 days). Major bleeding event rate was comparable (w/APS 8 [9.6%]; w/oAPS 462 [9.0%]). Conclusions: DOACs were used equally in long-term anticoagulation of VTE complicated with APS compared with VTE without APS, with better outcome.
Abstract 11735: The Effect of Different NLRP3 Inflammasome Inhibitors on High-Sensitivity C-reactive Protein in Patients After Percutaneous Coronary Intervention
Authors: Miao Yu, Zheng-Feng Zhu, Fen Yang, Yuan-Fan Yuan, Shu-De Liao, Mei-Lin Liu, xiang cheng
Journal: Circulation (2023)

Background: Colchicine treatment inhibits the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome assembly and reduces atherothrombotic cardiovascular events in coronary artery disease (CAD). However, the effects of other inhibitors targeting NLRP3 inflammasome needs further verification in CAD. Aims: This study aimed to investigate whether inhibitors targeting NLRP3 inflammasome besides colchicine are effective in patients after percutaneous coronary interventions (PCI). Methods: The study included 132 patients aged 18-80 years who completed the planned PCI and were treated with aggressive secondary prevention strategies for four weeks. The subjects were randomly assigned to one of the following treatment groups for four weeks: (1) control: no additional intervention; (2) colchicine: 0.5 mg once a day; (3) tranilast: 0.1 g thrice a day; or (4) oridonin: 0.5 g thrice a day. The primary outcome was the percentage change in hsCRP levels at the end of four weeks. Results: In total, 109 patients completed the study. The mean age was 58.33 years, 81 (74.31%) were male and 28 (25.69%) were female. The percentage changes in hsCRP after four weeks of treatment were -11.62%, -48.28%, -21.60%, and -7.81%, in the control, colchicine, tranilast, and the oridonin groups respectively. Compared with the control group, the colchicine group showed significantly greater reduction in hsCRP levels (P=0.022). The tranilast and oridonin groups did not show obvious changes. In targeted proteomic analysis, proteins associated with neutrophil activation (azurocidin,myeloperoxidase, myeloblastin), platelet aggregation (glycoprotein VI) and endothelial damage (galectin-3) were reduced with colchicine therapy. Conclusions: Colchicine could reduce hsCRP in patients after PCI, which is likely to act on neutrophils. Colchicine may still be the important choice for anti-inflammatory treatment of CAD.
Abstract 11896: Contribution of Amino Acid Transporter SLC7A5 to Pathological Ventricular Hypertrophy and Heart Failure
Authors: Javier Inserte, Sara Delgado, David Aluja, Elisabet Miro, Ignacio Ferreira, Jose A Barrabes
Journal: Circulation (2023)

Introduction: Transition from compensatory to pathological ventricular hypertrophy and heart failure (HF) is associated with metabolic remodeling. It has been described that hypoxia signaling induces the expression of the amino acid (AA) transporter SLC7A5 (LAT1) and the activation of its downstream pro-hypertrophic target mTORC1. Hypothesis: Chronic pathologic stimuli induce AA metabolism reprogramming comprising increased AA transport through LAT1, which plays a key role in the development of hypertrophy and its progression to HF. Methods: C57BL/6N mice were subjected to chronic pressure overload by constriction of the aorta (TAC). The selective LAT1 inhibitor JPH203 was chronically administered (ip) after TAC surgery. Dynamics of leucine were determined in heart samples from mice treated with 13C,15N-leucine using LC-MS/MS. Microarray-based gene expression profile, echocardiographic data, and markers of cardiac remodeling were measured at different time points. Results: Microarray results showed a profound AA metabolism remodeling consisting of a general increase in the expression of AA transporters, with LAT1 as the most overexpressed and reduced expression of enzymes involved in BCAA catabolism. Overexpression of LAT1 was confirmed in isolated cardiomyocytes. These changes correlated with a marked increase in labeled leucine uptake with respect to sham mice (310%), a moderate reduction in the formation of its ketoacid (51% α-ketoisocaproate), and potent inhibition of its catabolism (21% isovalerate and 13% 3-hydroxy-3-methyl-glutarate), and enhanced activation of mTOR pathway. Administration of JPH203 reduced leucine transport and mTOR activation, partially reversed the inhibition of BCAA catabolism, and attenuated hypertrophy and cardiac dysfunction induced by TAC. Conclusions: Pressure overload induces AA metabolic reprogramming characterized by enhanced AA transport and inhibited BCAA catabolism. LAT1 overexpression occurs in cardiomyocytes and contributes to adverse cardiac remodeling via mTOR pathway activation. We propose LAT1 inhibition as a novel therapeutic strategy against HF.