tbuckley/cabot-search huggingface dataset:
Abstract 13573: Association of Increased Eicosapentaenoic Acid to Arachidonic Acid Ratio With Early Restoration of Coronary Blood Flow in ST-Elevation Myocardial Infarction
Authors: Ryota Yamada, Takamitsu Nakamura, Takeo Horikoshi, Manabu Uematsu, Kazuyuki Yamaguchi, Tsuyoshi Kobayashi, Ryota Ando, Toru Yoshizaki, Yosuke Watanabe, Kenji Kuroki, Kazuto Nakamura, Akira Sato
Journal: Circulation (2023)

Background: Early restoration of coronary blood flow is important to reduce myocardial damage in patients with ST-elevation myocardial infarction (STEMI). Cardiovascular protection of increased levels of eicosapentaenoic acid (EPA) to arachidonic acid (AA) has been shown in recent clinical trials. Therefore, this study examined whether increased EPA / AA ratio was related to early restoration of coronary blood flow in STEMI patients underwent primary percutaneous coronary intervention (PCI). Methods: Serum levels of EPA, AA, and EPA/AA ratio were measured in consecutive 216 STEMI patients. The angiographic findings of TIMI-flow grade in the infarct related artery before PCI were compared between patients with and without increased EPA / AA ratio (&amp;gt;0.291). Results: TIMI-flow grade 3 before PCI were obtained in 25 (11.6%) of all study patients. Smaller enzymatic infarct size was obtained in patients with TIMI-flow grade 3 before PCI compared with TIMI-flow grade 0-2 before PCI (Peak CK-MB; 358 &amp;plusmn; 252 mg/dL, vs. 280 &amp;plusmn; 260 mg/dL, p &amp;lt;0.05). There were significant differences between 2 groups in the distribution of TIMI-flow grade (p&amp;lt;0.05). Moreover, multivariate logistic regression analysis showed that patients with increased EPA/AA ratio was significantly associated with the presence of TIMI-flow grade 3 before PCI after adjustment for conventional risk factors (OR 5.0, 95% CI 1.92-12.8, p&amp;lt;0.01). Conclusions: Increased levels of EPA /AA ratio is independently associated with early restoration of coronary blood flow, leading to reduced myocardial damage in patients with STEMI. These results might support the new strategy of administration of EPA before PCI in STEMI care.
Abstract 175: Adiponectin Alleviates Cortical Neuronal Apoptosis Following Cardiopulmonary Resuscitation by Attenuating MiR-31-5p Carried by Brain Microvascular Endothelial Cell-Derived Extracellular Vesicles
Authors: Yu Cao, Fating Zhou, Lu Gan, Peng Yao
Journal: Circulation (2023)

Background: Adiponectin (APN) is a cardiovascular-protective adipokine. Our previous research has shown that APN administration reduced cortical neuron apoptosis in mice after resuscitation. Brain microvascular endothelial cell-derived extracellular vesicles (BMEC-sEVs) have neuroprotective properties, and APN regulates BMEC-sEVs' function to alleviate neuronal apoptosis after resuscitation. However, the specific molecular mechanisms are unclear. MicroRNAs carried by sEVs play essential roles. Hypothesis: APN may alleviate cortical neuron apoptosis by regulating miRNAs carried by BMEC-sEVs. Aims: To investigate if APN attenuates cortical neuron apoptosis in mice after resuscitation by regulating BMEC-sEVs-miRNAs and to elucidate the underlying molecular mechanisms. Methods: BMEC-sEVs APN were extracted and identified. BMEC-sEVs were injected into the brain to establish a cardiopulmonary resuscitation mouse model, and cortical neuron apoptosis was assessed. Co-culture experiments were performed between BMEC-sEVs and primary cortical neurons, and apoptosis was evaluated after oxygen-glucose deprivation/reperfusion (OGD/R). Bioinformatics identified miRNAs with pro-apoptotic effects. APN-regulated specific BMEC-sEV miRNAs were screened. Overexpression and inhibition experiments confirmed the neuroprotective effects of the identified miRNA. Target genes were screened, and downstream signaling pathways were explored. Results: APN enhanced the protective effect of BMEC-sEVs against cortical neuron apoptosis. APN preconditioning reduced miR-155-5p and miR-31-5p levels in BMEC-sEVs APN . MiR-31-5p was highly expressed in primary BMECs and increased after OGD/R. Overexpression of miR-31-5p in cortical neurons aggravated neuronal apoptosis. Inhibition of miR-31-5p reduced apoptotic neurons in Adipoq -/- mice after ROSC. Map3k1 was the most affected target gene of miR-31-5p, and its regulatory role in cortical neuron apoptosis was confirmed. Conclusion: APN alleviates cortical neuron apoptosis after resuscitation by downregulating miR-31-5p expression in BMEC-sEVs; BMEC-sEVs APN alleviate cortical neuron apoptosis through the miR-31-5p/MAP3K1 signaling pathway.
Abstract 14276: Using Artificial Intelligence and Natural Language Processing on Electronic Health Records of Heart Failure Patients to Examine the Impact of Estimated Glomerular Filtration Rate Trend on Mortality
Authors: Monika Beles, Ana Moya, Clara L. Oeste, Imke Masuy, sofie verstreken, Riet Dierckx, Ward Heggermont, Jozef Bartunek, Dries Hens, Marc Vanderheyden
Journal: Circulation (2023)

Introduction and Hypothesis: Heart failure (HF) often leads to an imbalance between heart and kidney function, with a poor prognosis in HF patients linked to dynamic changes in renal function as well as chronic kidney disease (CKD). This study aimed to determine the incidence of reduced renal function upon HF diagnosis and to explore the potential for dynamic changes in kidney function to predict short- and long-term outcomes in a real-world cohort of HF patients. Methods: Clinical data of patients with a diagnosis of HF (index event) were gathered retrospectively using natural language processing. Patients were classified as having CKD based on their eGFR (&lt;60 mL/min/1.73m2) and a history of CKD and/or dialysis. eGFR trajectories were analyzed using linear mixed effects models. Cox proportional hazard models were used to analyze the relationship between baseline variables and mortality. Joint modeling was employed to assess the relationship between the eGFR trend and mortality. Results: There were 1986 patients in the study population, with a mean (SD) age of 74.8 ± 11.7 years and 58% of males. At the index event, 58% (n = 1156) had CKD, and 17% (n = 339) had HF with preserved ejection fraction (HFpEF). Median follow-up was 3.16 years. After 2 years, 10% (n = 198) of the patients had passed away. The proportion of CKD at index was considerably lower in the 2-year survivors group (55% vs 76%, p &lt; 0.001) in this group. The calculated mean annual eGFR reduction was 4.2 mL/min/1.73m 2 . Age, CVA, diastolic blood pressure, hemoglobin, HDL, potassium, and NT-proBNP levels in blood serum were found to be the primary predictors of mortality in multivariate Cox PH model. Joint modeling revealed that a current eGFR value that was 10 mL/min/1.73m 2 lower between patients corresponded with a higher mortality hazard of 1.22 ± 0.05 (p &lt; 0.001). In addition, a drop in eGFR of 10 mL/min/1.73m 2 over the previous year showed an the elevated mortality hazard of 1.97 ± 0.16 (p &lt; 0.001). Conclusions: We show that the prevalence of CKD is significant in a real-world population of HF patients, and CKD is a standalone predictor of mortality. Current eGFR value and the eGFR slope from the previous year have a potential to be used for individual mortality hazard assessment in the clinical follow-up of HF patients.
Abstract 15479: High Output Cardiac Failure Associated With Arteriovenous Fistula
Authors: Janina Quintero Bisono, Bistees George, Kori Ormachea
Journal: Circulation (2023)

Introduction: High output heart failure (HOHF) secondary to arteriovenous fistula (AVF) is known. However, having a high index of suspicion for the latter when encountering diuretic resistance in patients with a remote history of hemodialysis is key. Case A 68-year-old female with a history of kidney transplant in 2012 with no recent dialysis, hypertension, hyperlipidemia, pulmonary hypertension, heart failure with reduced ejection fraction, and atrial fibrillation presented with decompensated heart failure and acute kidney injury (AKI). Physical exam was remarkable for anasarca, and no apparent fistulas were noted. She was started on milrinone and furosemide drips. Clinical decision making Initial transthoracic echocardiogram (TTE) revealed an ejection fraction (EF) of 20%, which declined from 35%, along with new mitral and tricuspid regurgitation. Her hospitalization was complicated by altered mental status, worsening AKI requiring hemodialysis, atrial fibrillation with rapid ventricular response, and resistance to multiple diuretics and after-load reduction combinations. Diuretics and inotropic support were discontinued due to worsening clinical status. Given concerns for valvular disease, a transesophageal echocardiogram was obtained, confirming moderate to severe mitral and tricuspid valve regurgitation, bi-atrial enlargement, and reduced biventricular function. However, the patient was not clinically optimized for Mitra-clip. Further hemodynamics and volume status assessment with RHC revealed a mean PAP 44, PCWP 26, and CO 11 L/min. RHC results raised suspicion for HOHF. Interestingly, the patient was noted to have a right inguinal surgical scar with a palpable thrill, and an arteriovenous graft duplex revealed high volume flow. The patient underwent ligation of the right inguinal fistula. Repeat TTE two weeks post AVF ligation showed EF of 40% and improved functional mitral and tricuspid valve regurgitation. The patient ultimately was taken off hemodialysis and had clinically improved heart failure. GDMT was optimized, and outpatient evaluation for mitral valve intervention was scheduled. Conclusion Longstanding AVF can cause HOHF. Early index of suspicion is warranted for AVF ligation as it results in rapid EF recovery.
Abstract 17425: Matricellular Protein CCN1 Modulates Post-Infarct Scar Integrity and Structure
Authors: Annalara G Fischer, Erin M Elliott, Kenneth R Brittian, Julia W Aebersold, Nicholas C Tong, Yibing Nong, Steven P Jones, Joseph B Moore
Journal: Circulation (2023)

Introduction: Collagen deposition is required for repair of the heart following myocardial infarction (MI). As collagen abundance increases, so does its alignment, potentially influencing scar integrity. Because cell-matrix interactions regulate fibroblast behavior and matrix dynamics, adhesive factors, like cellular communication network (CCN) proteins, may contribute to post-MI scar formation. CCN1's role in skin collagen modulation and its recent emergence as a heart failure biomarker indicate its potential contribution to post-MI matrix remodeling. Consequently, we focused on CCN1 as a potential regulator of collagen organization. Hypothesis: CCN1 guides collagen alignment to support scar integrity via enhancing fibroblast-matrix interactions. Methods &amp; Results: Tamoxifen (TAM)-inducible Ccn1 fibroblast-specific KO ( Ccn1 -/- ) and control ( Ccn1 fl/fl ) mice (16-20 wk old) received TAM 3 wk prior to permanent coronary artery ligation. Cardiac function, heart mass, and scar structure were evaluated 1 wk post-MI using echocardiography, gravimetrics, and imaging techniques (picrosirius red, second harmonic generation, and transmission electron microscopy). Ccn1 -/- mice exhibited decreased survival (A) and an increased incidence of cardiac rupture compared to Ccn1 fl/fl (B-C). There were no differences in cardiac function or scar size among the groups. Macro- (E-F) and micro- (G) level structural analyses uncovered significant reductions in collagen organization in Ccn1 -/- mice. RNAi-mediated CCN1 depletion in fibroblasts resulted in reduced focal adhesion (FA) formation in culture (43.0 FA/cell ± 5.6 vs. 89.3 FA/cell ± 9.6; Mean ± SEM, p=0.0013, n=7), highlighting its role in facilitating fibroblast-ECM interactions. Conclusions: CCN1 is required for post-MI scar integrity. CCN1 may regulate fibroblast-ECM interactions to alter collagen organization.
Abstract 16482: Proteomic Measures Associated With Leisure-Time Physical Activity and Heart Failure Risk in Late-Life - The Atherosclerosis Risk in Communities Study
Authors: Sheila Hegde, Yimin Yang, Victoria Lamberson, Brian Claggett, Hicham Skali, Kelly R Evenson, Brian T Steffen, Joseph Coresh, Chiadi E Ndumele, Bing Yu, Amil M Shah
Journal: Circulation (2023)

Introduction: Leisure-time physical activity (LTPA) is associated with lower heart failure (HF) risk. However, the underlying molecular mechanisms by which LTPA impacts HF risk is unclear. Methods: We evaluated participants at Atherosclerosis Risk in Communities study visits 3 (1993-95) and 5 (2011-13) with plasma proteomics data (Somascan v4) and without HF or stroke. LTPA was assessed by the Baecke questionnaire as metabolic equivalent (MET)-minutes/week. We performed cross-sectional associations of 4,955 proteins with LTPA at visit 3 and then at visit 5 LTPA using multivariable quantile regression models at Bonferroni-corrected significance (p&lt;1e-5, p&lt;0.0004, respectively). We related these proteins to incident HF after visit 3 and then visit 5 using multivariable Cox regression models at Bonferroni-corrected significance (p&lt;0.00086, p&lt;0.003, respectively). Results: Thirty-nine proteins were associated with LTPA at visit 3 (n=10,402; age 60±6 yrs, 54% women; mean 688.6 MET-minutes/week, 773 incident HF events) and visit 5 (n=4,135; 75±5 yrs, 58% women; mean 834.8 MET-minutes/week, 362 events), of which 5 proteins were also associated with incident HF at both visits. Higher levels of THBS2, GABARAP, and BAGE2 were associated with lower LTPA and higher HF risk while higher levels of ART3 associated with higher LTPA and lower risk of incident HF (Figure). PTK7 demonstrated discordant associations with LTPA and HF risk. Levels of THBS2, GABARAP, BAGE2, and ART3 accounted for a significant proportion of the LTPA-HF association (p&lt;0.05). Conclusion: Large-scale proteomics can identify novel biomarkers potentially linking LTPA to HF risk. Further study is needed of THBS2, GABARAP, BAGE2, and ART3, which may link the association of LTPA on HF.
Abstract 16711: Outcomes of Severe Mitral Stenosis With the Revised Severity Criteria: Mitral Valve Replacement versus Percutaneous Mitral Valvuloplasty
Authors: Dae-Young Kim, Iksung Cho, Kyu Kim, Seo-Yeon Gwak, Kyungeun Ha, Hee Jeong Lee, Kyu-Yong Ko, Chi Young Y Shim, Jong-Won Ha, William Kim, In-Jai Kim, Seonhwa Lee, Incheol Kim, KANGUN CHOI, Hojeong Kim, Jang-Won Son, Geu-Ru Hong
Journal: Circulation (2023)

Introduction: Mitral stenosis (MS) severity is determined by mitral valve area (MVA); the threshold for severe MS was raised from MVA of 1.0 cm 2 to 1.5 cm 2 in recent guidelines. Hypothesis: This study aimed to compare the clinical outcomes, according to percutaneous mitral valvuloplasty (PMV) versus mitral valve replacement (MVR) treatment strategy, of severe MS patients with the updated criteria for the subgroups categorized by MVA of 1.0 cm 2 and 1.5 cm 2 . Methods: From the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry of 3,140 patients, we included severe MS patients who underwent PMV or MVR between January 2000 and December 2021 except previous valvular surgery/intervention, at least moderate other valvular dysfunction, and thrombus at the left atrium/appendage. Moderately severe MS (MS-MS) and very severe MS (VS-MS) were defined as 1.0 cm 2 &lt;mva≤1.5 cm2 and MVA≤1.0 cm 2 , respectively. Primary outcomes were a composite of cardiovascular (CV) death and heart failure (HF) hospitalization. Secondary outcomes were a composite of primary outcomes and redo-intervention. Results: Among 442 patients (mean 56.5±11.9 years, women 77.1%), the MVR group (n=260) was older, had more comorbidities, higher echoscore, larger left chambers, and higher right ventricular systolic pressure than the PMV group (n=182). During a mean follow-up of 6.9±5.2 years with inverse probability weighted matching, primary outcomes did not differ, but the MVR group experienced fewer secondary outcomes (p=0.010). In subgroup analysis of MS-MS and VS-MS patients, primary outcomes did not differ. However, the MVR group in VS-MS patients showed better secondary outcomes (p=0.012) (Figure). Conclusions: PMV or MVR did not influence CV mortality or HF hospitalization in both MS-MS and VS-MS. However, due to increased early redo-intervention in the PMV group in VS-MS, MVR would be the preferable option without clear evidence of suitable morphology for PMV.
Abstract 15226: Premature Ventricular Complexes Were Not Associated With an Increased Risk of Atrial Fibrillation in Patients Without Structural Heart Disease
Authors: Robin Bouleau, Natalie Glaser, Martin Jonsson, Raffaele Scorza
Journal: Circulation (2023)

Background: Recent studies have suggested that patients with premature ventricular complexes (PVCs) may have a higher risk for atrial fibrillation. However, the study bases are heterogenous, and it is currently unclear whether frequent PVCs are linked to an increased risk in patients where underlying structural heart disease has been thoroughly excluded. Research question: Do PVCs increase the risk of atrial fibrillation in patients without structural heart disease? Aim: To analyze the risk of new-onset atrial fibrillation in PVC patients without structural heart disease. Methods: We included PVC patients from three secondary centers in Stockholm, Sweden. The patients had no history of heart disease, normal results at exercise stress test and echocardiography, and no previous diagnosis of atrial fibrillation. For each case, four age- and sex-matched controls were obtained from the general population. Controls with previous heart disease or atrial fibrillation were excluded. We used inverse probability of treatment weighting (IPTW) to control for differences in baseline characteristics between the groups. An IPTW cause-specific hazards model was fitted using the cmprskcoxmsm package in R. Data are presented as hazard ratios (HR) with 95% confidence intervals (CI). Results: A total of 773 PVC patients and 3128 controls were included. The median age was 59 years, and 2285 (59%) were women. Patients with PVCs had a higher incidence of malignant diseases, hypertension, and hyperlipidemia. After inverse probability of treatment weighting, baseline characteristics were well-balanced between the groups. The median follow-up time was 5.2 years (maximum 6.5 years). The risk for atrial fibrillation was higher for patients with PVCs in the crude cohort (4.3% versus 2.0%), but there was no difference between the groups in the IPTW cohort after adjusting for death as competing risk (HR 1.50, 95% CI 0.88-2.57, p=0.14). Conclusion: PVC patients without structural heart disease did not have a higher risk of incident atrial fibrillation than age- and sex-matched controls from the general population. These results could argue against a causal relationship between PVCs and atrial fibrillation. However, more studies are needed to confirm the results.
Abstract 17626: Apolipoprotein A-IV-Associated Cardiac Amyloidosis: A Classic Presentation of a Rare Condition
Authors: Samuel B Wopperer, Marie Christine Aubry, Martha Grogan, Michael W Cullen
Journal: Circulation (2023)

Introduction: A 65-year-old male with type one diabetes mellitus underwent a pancreas and kidney transplant approximately seven years ago and has received chronic tacrolimus. He presented with subacute dyspnea on exertion, orthopnea, and edema. His background also includes ongoing chronic kidney disease stage 3A, orthostatic hypotension, and spinal stenosis. On exam, he had abdominal and lower extremity swelling. An echocardiogram showed preserved LVEF, concentric hypertrophy, hyperrefractile myocardium, reduced longitudinal strain with apical sparing, and a tiny pericardial effusion. Hypothesis: His echocardiogram indicated an infiltrative process such as amyloidosis or tacrolimus cardiotoxicity or possibly hypertrophic cardiomyopathy. Methods: Free light chains and protein studies with mass-fixation demonstrated no monoclonal gammopathy. PYP scan was negative for transthyretin amyloidosis. A cardiac MRI showed patchy subendocardial and midmyocardial delayed gadolinium enhancement, supporting the clinical suspicion for cardiac amyloidosis. With the need to exclude tacrolimus toxicity as well, subsequent endomyocardial biopsy revealed apolipoprotein A-IV-associated cardiac amyloidosis (Figure 1). Results: Apolipoprotein A-IV-associated cardiac amyloidosis occurs in about 0.6% of patients with cardiac amyloid and has classic manifestations of LV outflow obstruction, microvascular disease, and especially renal insufficiency. When these features occur in patients with clinical and imaging findings suggesting cardiac amyloidosis despite negative testing for more common types of amyloidosis, clinicians should proceed with endomyocardial biopsy to evaluate for less common forms. Conclusions: We report a rare case of apolipoprotein A-IV-associated cardiac amyloidosis. This case highlights the need for endomyocardial biopsy when clinical suspicion for cardiac amyloidosis persists despite negative testing.
Abstract 16494: Cardiac Structure and Function Predict Incident Atrial Fibrillation and Flutter in Patients With HFpEF - Lessons From PARAGON-HF
Authors: Sheng Nan Chang, Henri Lu, Maja Cikes, Brian Claggett, Riccardo M Inciardi, Amil M Shah, Carolyn S Lam, Akshay S Desai, Scott Solomon, Sheila Hegde, Hicham Skali
Journal: Circulation (2023)

Introduction: Incident atrial fibrillation and flutter (AFF) are common among patients with heart failure with preserved ejection fraction (HFpEF) portending a worse prognosis. Cardiac echocardiographic predictors of incident AFF in patients with HFpEF are not well known. Methods: Patients without history of AFF enrolled in the echocardiographic sub-study of the PARAGON-HF trial with adequate image quality were included in this analysis. Cardiac structure and function parameters were measured per the American Society of Echocardiography guidelines. Incident AFF was ascertained during serial trial visits. Multivariable Cox proportional hazards models were used to identify parameters of echocardiography associated with incident AFF and were adjusted for variables previously known to associate with incident AFF (age, heart rate, body mass index and NT-pro-BNP). Results: Among patients without prior AFF (N=425, 54% women, mean age 71 ± 8 years), 63 developed incident AFF over a median follow-up of 2.8 years (5.4 per 100 person-years). After multivariable adjustment, higher left atrial (LA) volume index (HR: 1.35 per 11.3 ml/m 2 , 95% CI: 1.10-1.66, p=0.004), left ventricular mass index (HR: 1.40 per 25.7 g/m 2 , 95% CI: 1.09-1.80, p=0.008), septal E/e’ ratio (HR: 1.72 per 6.4 units, 95% CI: 1.29-2.28, p&lt;0.001), and lower septal a’ (HR: 0.48 per 2.0 cm/s, 95% CI: 0.33-0.70, p&lt;0.001) were associated with a significantly higher risk of incident AFF. Furthermore, higher (better) LA reservoir strain (LAsr) (HR: 0.66 per 10.8%, 95% CI: 0.48-0.92, p=0.014) and LA contractile strain (absolute LAsct) (HR: 0.71 per 6.7%, 95% CI: 0.51-0.98, p=0.040) predicted lower risk of incident AFF. Conclusions: In the PARAGON-HF echocardiographic sub-study, worse diastolic and LA function, larger LA size and higher LV mass were associated with a higher risk of incident AFF.