tbuckley/cabot-search huggingface dataset:
Abstract 16133: Lipoprotein(a) Screening Practices in a Large US Healthcare Dataset
Authors: Mary P McGowan, Dianne E MacDougall, Xingdi Hu, Wess Boatwright, WILLIAM HOWARD, Yuliia Puhach, Halyna Malchyk, Katherine A Wilemon
Journal: Circulation (2023)

Introduction/Background: Elevated Lipoprotein(a) [Lp(a)] is an independent, genetically determined, causal risk factor for atherosclerotic cardiovascular disease (ASCVD). European and Canadian guidelines recommend Lp(a) screening in all adults, while US guidelines recognize elevated Lp(a) as a risk enhancer. Research Hypothesis: Although elevated Lp(a) is an important ASCVD risk factor with a high prevalence, testing is infrequent. Aims: To characterize adults screened for Lp(a) and their clinicians using real-world data from the Family Heart Database of &gt;324M US individuals with medical and/or lab data from 2012-2021. Methods: In this retrospective cohort study of &gt; 44 million adults with lab data and medical claims one year before and after initial Lp(a) measurement, screening rates, demographics, ASCVD status, comorbidities, Lp(a) level (median; IQR) and ordering clinician are described. Results: Lp(a) screening rates were 1.1% (n=500,899 of 44,857,734) and 2.0% (n=218,331 of 10,658,820) in all and in those with ASCVD respectively. Among those with any Lp(a) test, median age was 60 (IQR 50-69) years, 55.0% were female,43.6%, 33.0%, 33.9%, and 13.9% had prior ASCVD, hypertension, hyperlipidemia and diabetes respectively. 20% had an Lp(a) level &gt; 139 nmol/L. Lp(a) level was higher in females than males 36 (IQR 11-118) versus 28 (IQR 10-95) nmol/L, and in Blacks versus White and Hispanic populations 73 (IQR 24-170), 29 (IQR 10-102) and 28 (IQR 10-85) nmol/L. A small number of clinicians (n=687 of 41,976; 1.6%) ordered 50% of Lp(a) tests. Conclusions: Measurement of Lp(a) in US adults with and without ASCVD was rare but increased substantially after 2018. Individuals who had Lp(a) assessed were older and frequently had ASCVD and comorbidities. A small number of clinicians were responsible for most Lp(a) orders. Additional research into barriers and facilitators of Lp(a) screening is needed.
Abstract 17891: Underutilization of Palliative Care Consults and End-of-Life Care Planning After Cardiogenic Shock
Authors: Smrithi Sukumar, Serena Verma, Oksana Chubrikova, Alyssa Ramsay, Abdurahman Khalil, Haider Warraich, Van-Khue Ton
Journal: Circulation (2023)

Background: Cardiogenic shock (CS) is associated with significant mortality. The 2022 ACC/AHA/HFSA guidelines discuss the importance of palliative care (PC) in advanced heart disease, but PC and end-of-life care (EOLC) integration after CS is not well characterized. We aimed to study the use of PC and EOLC planning after CS. Hypothesis: We assessed the hypothesis that PC consults and EOLC planning are underutilized after CS. Methods: This is a retrospective observational study of 63 consecutive patients at a quaternary care center in Boston diagnosed with CS between January and April 2022. CS onset and etiology were adjudicated by treating physicians. Results: Of 63 patients with CS (mean age 61±14 years, 30% Female, 73% White), 26 (41%) died during admission and 31 (49%) survived 1 year after CS onset. Only 6 patients (10%) received PC consults for EOLC considerations (consults placed on average 9 days from CS onset) (Table 1). Only 24 (38%) had documented advanced care plans after developing CS, of which 14 were documented by PC consultants. Of 44 patients with MCS or ICD placed, only 1 had a documented discussion about the option of discontinuing the therapy in the future. After CS, 28 (44%) had changes in resuscitation limits. Only 1 patient had their preferred location of death documented. Palliative inotropes were prescribed to 2 patients at discharge, and 3 patients were discharged to hospice. Readmission rates at 3 and 6 months were 24% and 36%, respectively. Conclusions: PC and EOLC planning are underutilized after CS, despite the significant mortality of CS. Secondary PC models may not be optimal for CS, given the acute presentation of CS and bimodal distribution of survival after onset. These data demonstrate a compelling need to address key considerations that impact EOLC after CS, such as resuscitation limits, duration of advanced therapies, and goal-concordant discharge locations. Further research is needed to explore optimal models of PC and EOLC integration after CS.
Abstract 15430: Dramatic Reduction in Lipoprotein(a) With Immunosuppressant, Anti-Inflammatory, and Antimicrobial Therapy in a Patient With Multiple Inflammatory Diseases
Authors: Donya Mazdeyasnan, Michael J Wilkinson
Journal: Circulation (2023)

Background: Lipoprotein(a) (Lp(a)) is a potent, causative risk factor for ASCVD. Patients with inflammatory and autoimmune diseases are also at increased ASCVD risk. There is a complex, incompletely understood relationship between inflammation and Lp(a), including observations that IL-6 induces LPA gene expression. We present a unique case of dramatic Lp(a) lowering occurring with a combination of immunosuppressing, anti-inflammatory, and antimicrobial therapies. Case: A 50-year-old Black woman was referred to Lipid Clinic for Lp(a) of 138 mg/dL. Medical history included Crohn’s disease, total colectomy and end ileostomy, seronegative inflammatory polyarthropathy with psoriatic arthritis, and reactive neutrophilic dermatosis with suspected bowel-associated dermatitis-arthritis syndrome (BADAS). CT coronary calcium score was 0 Agatston units, but plaque was visible in her right coronary artery below the threshold for quantification. With rosuvastatin 5mg daily (which can increase Lp(a)), she experienced a ~25% reduction in LDL-C (baseline 102 mg/dL). She was not treated with niacin or PCSK9 inhibitors. Over the course of ~2.5 years, as the patient experienced BADAS flares she received extensive immunosuppressing, anti-inflammatory, and antimicrobial treatment including adalimumab (TNF-alpha inhibitor), sulfasalazine, dapsone, and doxycycline, and her Lp(a) decreased from 138 mg/dL to a low of 48 mg/dL (65% reduction) (Figure). Conclusion: Previous studies have shown that certain immunosuppressing therapies may lower Lp(a), and in this unique case we observed a dramatic reduction in Lp(a) during treatment with a complex regimen of immunosuppressing, anti-inflammatory, and antimicrobial therapies in a patient experiencing frequent flares of inflammatory diseases. The relationship between Lp(a), systemic inflammation, and the potential effects of anti-inflammatory and immunosuppressive therapies on Lp(a) deserves further study.
Abstract 15295: Myocardin Condensation Drives Cell Lineage Specification During Cardiogenesis
Authors: Peiheng Gan, Mikayla Eppert, Nancy De La Cruz, Reshma Veettil, AKANSHA SHAH, Prashant Pradhan, Svetlana Bezprozvannaya, Rhonda S Bassel-Duby, Ning Liu, Eric N Olson, Benjamin R Sabari
Journal: Circulation (2023)

During cardiovascular development, cells make switch-like decisions to activate the expression of new gene programs leading to lineage specification. The mechanisms underlying these decisive choices remain unclear. Myocardin is a cardiomyocyte and smooth muscle cell specific transcriptional coactivator, which is necessary and important for activating cardiovascular genes. We show that Myocardin activates lineage-specific gene programs by concentration-dependent and switch-like formation of nuclear condensates. By modeling the natural changes in Myocardin concentration during development, coupled with quantitative fluorescence microscopy, single-cell resolution reporter assays, and cellular differentiation assays, we demonstrate that condensate formation is directly linked to transcriptional activation and cardiovascular lineage specification. During cardiomyocyte and smooth muscle cell differentiation, the formation of Myocardin condensates precedes activation of cell identity genes and these condensates are present at sites of cell identity gene transcription. Myocardin condensates form, activate gene expression, and specify cell state at critical concentration thresholds, dependent upon the C-terminal disordered region of Myocardin. Disrupting condensate formation by manipulating the sequence of this region abolishes gene activation, which can be rescued by replacing this region with condensate-forming disordered regions from other unrelated proteins. Our work demonstrates that Myocardin condensation at critical concentrations enables switch-like changes in gene expression programs, providing new insights into cardiomyocyte and smooth muscle cell lineage specification during cardiovascular development.
Abstract 15885: A Masquerading Early Beat Induces Ventricular Fibrillation
Authors: Juergen H Kloo, David B Laslett, Melissa Gunchenko, Edmond Cronin
Journal: Circulation (2023)

Clinical Case: A 51 year old male with a history of hypertension, G6PD deficiency, thrombotic thrombocytopenic purpura, prior stroke, and morbid obesity presented with resuscitated out of hospital VF arrest. Electrolytes and ECG were normal. During his admission, the patient had two VF events that were induced by what appeared to be a short coupled right bundle branch block (RBBB) morphology PVC. He was brought to the electrophysiology lab for PVC ablation and ICD implantation. Baseline rhythm was sinus with what appeared to be both RBBB morphology PVCs and junctional extrasystoles. With both extrasystoles, the His potential preceded the QRS by 50 ms, and atrial activation in the His catheter and coronary sinus catheter was also earlier than the QRS. Activation mapping of the right bundle showed later activation than the His potential. This was all consistent with junctional premature complexes (JPC) with frequent RBBB aberrancy rather than fascicular PVCs. Slow pathway modification was performed to attempt to ablate the JPCs. After multiple ablations along the tricuspid annulus and back to the coronary sinus os that triggered slow junctional beats, the patient’s JPC burden was significantly reduced. An ICD was also implanted. The patient was discharged on flecainide. At 4 month follow up he had not had recurrence. Discussion: Early coupled PVCs are a well-known cause of ventricular fibrillation, but JPCs inducing VF have not been described previously. Placement of a coronary sinus and His catheter helped identify early that this was not simply a fascicular PVC. This case demonstrates the importance of keeping a broad differential diagnosis when starting any EP study. Ablating the slow pathway area can be effective to treat JPCs while preserving native AV conduction as demonstrated in this case.
Abstract 15501: Effects of Vericiguat on Right Ventricular Function in Chronic Heart Failure Patients
Authors: Gregor Poglajen, Sabina Frljak, Neza Zorz, Tine Bajec, Andraz Cerar, Gregor Zemljic, Renata Okrajsek, Miran SEBESTJEN, Bojan Vrtovec
Journal: Circulation (2023)

Introduction: Despite the beneficial clinical effects of vericiguat in chronic heart failure, the potential effects of vericiguat therapy on right ventricular (RV) function remain poorly defined. Hypothesis: We sought to evaluate the effects of vericiguat on RV function in chronic heart failure patients. Methods: We performed a prospective non-randomized single center study enrolling 24 consecutive HFrEF outpatients who were receiving stable heart failure therapy for at least 3 months. All patients received vericiguat 2,5 mg qd at baseline and up-titration was performed on a bi-weekly basis to the target dose of 10 mg qd. At baseline and at 3 month follow-up all patients underwent clinical, biochemical and echocardiographic evaluation. Improved RV function was defined as any improvement in TAPSE between baseline and 3 months. Results: During follow-up we observed a significant overall improvement of TAPSE (18.5±4.2 mm vs. 21.3±4.7 mm; P=0.03) and TR gradient (35±10 mmHg vs. 29±8 mmHg; P=0.04). RV function improved in 17 patients (70%; Group A) and remained unchanged in 7 (30%) patients (Group B). At baseline, the two groups did not differ in gender (male; 100% in Group A vs. 90% in Group B; P=0.37), age (64±9 years vs. 61±9 years; P=0.59), NYHA class (2.9±0.5 vs. 3.1± 0.3; P=0.39), or heart failure etiology (ishemic: 64% vs. 71%; P=0.76). Heart failure therapy was also comparable: ARNI (94% vs. 100%; P=0.53), beta blockers (94% vs. 100%; P=0.53), MRA (100% vs. 100%), SGLT2i (100% vs. 86%; P=0.12) and loop diuretics (59% vs. 57%; P=0.94). We found no differences in baseline LVEF (30±6% vs. 29±4%; P=0.73), LVOT VTI (15±3 cm vs. 14±5 cm; P=0.34), LVEDV (219±51 mL vs. 197±56 mL; P=0.39), TAPSE (17±3 mm vs. 18±3; P=0.68), RVIDd (39±4 mm vs. 38±3 mm; P=0.58) and TR gradient (34±8 mmHg vs. 38±11 mmHg; P=0.38). Both groups received similar doses of vericiguat (8.5±2.8 mg in Group A vs. 6.8±2.9 mg in Group B; P=0.19). Compared to Group B, we found significantly lower baseline NT-proBNP serum levels in Group A (1888±1973 pg/mL vs. 6373±5465 pg/mL; P=0.009). Conclusions: Vericiguat therapy may be associated with improved RV function in chronic heart failure patients. The effects appear to be particulary pronounced in patients with lower NT-proBNP levels.
Abstract 16746: Novel Role of Endothelial CD45 in Regulating Endothelial-to-Mesenchymal Transition (EndMT) in Atherosclerosis
Authors: Qianman Peng, Bo Zhu, Yao Wei Lu, Kui Cui, Bandana Singh, Kathryn Li, Jill Wylie-Sears, Daniel Osorio, Liang Sun, Scott Wong, Douglas B Cowan, Joyce E Bischoff, Hong Chen
Journal: Circulation (2023)

Introduction: Atherosclerosis is the leading cause of mortality in the United States and most other developed countries. Endothelial cell (EC) activation is a hallmark of the initiation and progression of atherosclerosis; identification of molecular markers of dysfunctional endothelium represents a biological challenge to developing new therapeutic targets. CD45 is a marker of hematopoietic cells, which is rarely expressed in ECs. However, recent studies indicated that CD45 is indispensable in driving the endothelial-to-mesenchymal transition (EndMT) following myocardial infarction. EndMT has also been implicated in the pathogenesis of atheroma progression. Thus, we aim to investigate whether endothelial CD45 contributes to the progression of atherosclerosis by facilitating the EndMT. Methods and results: In vitro , we used CRISPR/inactive Cas9 transcriptional activation system to express CD45 in human endothelial colony-forming cells (ECFCs). Using FACS analyses, we found that CD45+ECFCs upregulate transforming growth factors (TGFβ 1-3 ) that implicate EndMT but downregulate FGFR1 expression, which exacerbates EndMT. qRT-PCR and WB showed that CD45+ECFCs downregulate transcription factors KLFs. In vivo , we generated a tamoxifen-inducible EC-specific CD45 deficient mouse strain (EC-CD45iKO) in ApoE-deficient (ApoE-/-) background and fed with a Western diet (C57BL/6) for atherosclerosis and molecular analyses. We found that ApoE-/- / EC-iCD45KO mice reduced plaque macrophages, foam cells, expression of adhesion molecule, and lesion development compared to ApoE-/- controls. Interestingly, ApoE-/- / EC-iCD45KO mice showed the reduction of α-smooth muscle actin, which is typical of EndMT, in the aortic plaque. Single-cell RNA-seq analyses have been performed to characterize that endothelial CD45 regulates the expression of pro-inflammatory, EndMT, and endothelial cell markers genes on the aortic ECs. Conclusion: These findings demonstrate that endothelial CD45 potentiates atherosclerosis by inducing TGF signaling and mesenchymal phenotype, causing FGFR1 downregulation and attenuating KLFs expression to drive EndMT, highlighting endothelial CD45 may be a new drug target for the treatment of atherosclerosis.
Abstract 13350: Bivalirudin versus Heparin in Patients With Myocardial Infarction, an Updated Meta-Analysis
Authors: Abdulrhman Khaity, Nada Mostafa Al-dardery, Aya Ehab Abd-Alwahed, Ahmed K. Awad, Ayman K. Awad, Ambreen Nabeel, Syed Karam Gardezi, Rehmat Ullah Awan
Journal: Circulation (2023)

Bivalirudin and heparin are anticoagulant drugs commonly used in patients with acute myocardial infarction who undergo percutaneous coronary intervention (PCI). We performed this meta-analysis to update the present evidence about the safety and efficacy of bivalirudin versus heparin in myocardial infarction patients who underwent PCI. We searched PubMed, Web of Science, Cochrane Central Register of Controlled Trials, and Scopus for relevant randomized controlled trials (RCTs) from inception until 1 April 2023. Records were screened for eligible studies, and all relevant outcomes were pooled as the risk ratios (RR) with the corresponding 95% confidence intervals (CI) in the meta-analysis models using Review Manager (RevMan version 5.4). Pooling data from 9 RCTs (20,036 patients) showed that bivalirudin was superior to heparin in terms of adverse major cardiovascular and cerebrovascular events (MACE) (RR 0.78, 95% CI 0.62 to 0.99, P=0.04) and stent thrombosis (RR 0.73, 95% CI 0.60 to 0.89, P=0.002). However, the overall effect did not favor either of the two groups in terms of all-cause death (RR 1.09, 95% CI 0.90 to 1.30, P=0.37), myocardial infarction (RR 0.87, 95% CI 0.71 to 1.07, P=0.2), stroke (RR 1.09, 95% CI 0.77 to 1.54, P=0.6), bleeding (RR 0.97, 95% CI 0.88 to 1.07, P=0.5), and Bleeding Academic Research Consortium (BARC) scale type 2 (RR 0.93, 95% CI 0.82 to 1.06, P=0.3). Ultimately, the current evidence suggests that bivalirudin appears to be an effective alternative to heparin for anticoagulation during PCI in myocardial infarction patients in terms of MACE and stent thrombosis. Further research is needed to determine the optimal anticoagulation strategy.
Abstract 16166: Self-Care Self-Efficacy Predicts Long-Term Health-Related Quality of Life in Patients With Heart Failure
Authors: Akiko Okada, Kanako Hayashi, Miyuki Tsuchihashi-Makaya
Journal: Circulation (2023)

Introduction: Health-related quality of life (HRQOL) influences prognosis in heart failure (HF). Self-care and self-care self-efficacy are important in improving HRQOL; however, their effect on long-term HRQOL is yet to be elucidated. Aims: To determine the effect of self-care and self-care self-efficacy on long-term HRQOL in patients with HF. Methods: This longitudinal study enrolled outpatients with HF, who were followed-up at 3, 6, and 12 months. Self-care and self-care self-efficacy were assessed using the Self-Care of Heart Failure Index ver.7.2 and the Self-care Self-Efficacy scale, respectively. HRQOL was assessed using the Patient-Reported Outcomes Measurement Information System. Linear regression analysis was conducted to determine the association between baseline self-care and self-care self-efficacy and physical and mental dimensions of HRQOL at each time period. Adjusted variables were age, sex, body mass index, HF severity, comorbidities, activities of daily living, marital status, education level, and depressive symptoms. Results: This study analyzed 315 patients (mean age, 73±13 years, 72% male). The physical dimensions of HRQOL at all time points were associated with baseline self-care self-efficacy (baseline, 3, 6, and 12 months: p &lt; 0.001, p &lt; 0.001, p &lt; 0.001, and p &lt; 0.001, respectively) but not with baseline self-care maintenance (p = 0.057, p = 0.108, p = 0.101, and p = 0.153), symptom perception (p = 0.111, p = 0.101, p = 0.662, and p = 0.944), and self-care management (p = 0.737, p = 0.229, p = 0.387, and p = 0.167). The mental dimension of HRQOL at all time points were associated with self-care self-efficacy (baseline, 3, 6, and 12 months: p &lt; 0.001, p &lt; 0.001, p &lt; 0.001, and p &lt; 0.001, respectively). Multivariate linear regression analysis revealed that high scores on the physical and mental dimensions of HRQOL at all time points were significantly associated with high baseline self-care self-efficacy despite adjustment for all variables (physical and mental dimensions: baseline, p &lt; 0.001 and p &lt; 0.001; 3 months, p &lt; 0.001 and p &lt; 0.001; 6 months, p &lt; 0.001 and p &lt; 0.001; 12 months, p &lt; 0.001 and p &lt; 0.001). Conclusion: Improving self-care self-efficacy is important for maintaining long-term HRQOL in patients with HF.
Abstract 13169: Different 90-day Readmission Outcomes Among Cardiogenic Shock Survivors Based on Their Index Hospitalization Etiology
Authors: Boyangzi Li, Lingling Wu, Neal Olarte, Carlos Alfonso, Jason N Katz, Jacob C Jentzer
Journal: Circulation (2023)

Background: Up to 70% of patients with cardiogenic shock (CS) will survive hospitalization, yet studies on the outcomes of CS survivors are scarce. Hypothesis: We hypothesized that CS survivors would be at high risk of rehospitalization, particularly CS without acute myocardial infarction (AMI) who may have chronic heart failure (HF). Methods: We used the Nationwide Readmissions Database (NRD) to examine adult patients who were discharged alive after an index CS admission from 2016-2019. We compared demographic and clinical features during the index admission and the readmission mortality rate between the AMI-CS versus non-AMI-CS groups. We analyzed the cumulative hazard for all-cause readmission within 90 days after index hospitalization using Kaplan-Meier curves. Results: We included 134,793 survivors of CS hospitalization from 2016 to 2019 who were discharged to home or a long-term facility, including 43.9% with AMI-CS and 56.1% with non-AMI-CS. The demographics and clinical features differed between the AMI-CS and non-AMI-CS groups, with more HF and non-cardiac comorbidities in the non-AMI-CS group. The non-AMI-CS patients were more likely to be readmitted after discharge, with a higher 90-day readmission rate compared to the AMI-CS group (31.6% vs 25.9%, p &lt;0.001; Figure). During the readmission, the non-AMI-CS group had a higher rate of repeat CS presentation compared to the AMI-CS group (8.9% vs.. 6.1%, p &lt; 0.001). In-hospital mortality during readmission was higher in the non-AMI-CS group (8.6% vs.7.2%, p &lt; 0.001). Conclusions: Nearly one-third of CS survivors require readmission within 90 days after their index hospitalization. Non-AMI-CS patients have a higher re-admission rate after their index hospitalization and worse outcomes during readmission. This analysis identifies an unmet need and an important opportunity to improve long-term outcomes for CS survivors.