tbuckley/cabot-search huggingface dataset:
A Proteomics-Based Approach for Prediction of Different Cardiovascular Diseases and Dementia
Authors: Frederick K. Ho, Patrick B. Mark, Jennifer S. Lees, Jill P. Pell, Rona J. Strawbridge, Dorien M. Kimenai, Nicholas L. Mills, Mark Woodward, John J.V. McMurray, Naveed Sattar, Paul Welsh
Journal: Circulation (2024)

BACKGROUND: Many studies have explored whether individual plasma protein biomarkers improve cardiovascular disease risk prediction. We sought to investigate the use of a plasma proteomics-based approach in predicting different cardiovascular outcomes. METHODS: Among 51 859 UK Biobank participants (mean age, 56.7 years; 45.5% male) without cardiovascular disease and with proteomics measurements, we examined the primary composite outcome of fatal and nonfatal coronary heart disease, stroke, or heart failure (major adverse cardiovascular events), as well as additional secondary cardiovascular outcomes. An exposome-wide association study was conducted using relative protein concentrations, adjusted for a range of classic, demographic, and lifestyle risk factors. A prediction model using only age, sex, and protein markers (protein model) was developed using a least absolute shrinkage and selection operator–regularized approach (derivation: 80% of cohort) and validated using split-sample testing (20% of cohort). Their performance was assessed by comparing calibration, net reclassification index, and c statistic with the PREVENT (Predicting Risk of CVD Events) risk score. RESULTS: Over a median 13.6 years of follow-up, 4857 participants experienced first major adverse cardiovascular events. After adjustment, the proteins most strongly associated with major adverse cardiovascular events included NT-proBNP (N-terminal pro B-type natriuretic peptide; hazard ratio [HR], 1.68 per SD increase), proADM (pro-adrenomedullin; HR, 1.60), GDF-15 (growth differentiation factor-15; HR, 1.47), WFDC2 (WAP four-disulfide core domain protein 2; HR, 1.46), and IGFBP4 (insulin-like growth factor-binding protein 4; HR, 1.41). In total, 222 separate proteins were predictors of all outcomes of interest in the protein model, and 86 were selected for the primary outcome specifically. In the validation cohort, compared with the PREVENT risk factor model, the protein model improved calibration, net reclassification (net reclassification index +0.09), and c statistic for major adverse cardiovascular events (+0.051). The protein model also improved the prediction of other outcomes, including ASCVD ( c statistic +0.035), myocardial infarction (+0.023), stroke (+0.024), aortic stenosis (+0.015), heart failure (+0.060), abdominal aortic aneurysm (+0.024), and dementia (+0.068). CONCLUSIONS: Measurement of targeted protein biomarkers produced superior prediction of aggregated and disaggregated cardiovascular events. This study represents an important proof of concept for the application of targeted proteomics in predicting a range of cardiovascular outcomes.
Abstract 4145209: Death on Admission- Characterizing 30-Day Mortality in Patients Admitted to the Coronary Care Unit for Heart Failure Following the COVID-19 Pandemic
Authors: Tejal Ghadiali, Pratik Doshi, Anushka Das, Stephanie Jinno, Michael Fong
Journal: Circulation (2024)

Background: Acute decompensated heart failure accounts for an increasing proportion of hospitalizations in the United States and is linked to high readmission and 30-day mortality rates. Prior studies suggest up to 17% mortality rate within 30 days for patients admitted with heart failure. Research Questions/Hypothesis: We present an analysis characterizing patients who experienced mortality within 30 days of admission at a large safety net hospital following the COVID-19 pandemic. Methods/Approach: A retrospective review was conducted for all heart failure admissions of patients &gt; 18 years of age admitted to the coronary care unit (CCU) at Los Angeles General Medical Center from January to December 2021 after the peak of the COVID-19 pandemic. Demographics, insurance information, drug use, medication use, heart failure etiology, and CCU interventions were indexed. The primary outcome was all-cause mortality. Results/Data: 172 patients were identified during the study period. 10% of patients died within 30 days of admission, of which 94% died during the same admission. Of patients who died during index admission, 88% had heart failure with reduced EF. None of these patients were on all four pillars of guideline-directed medical therapy (GDMT), with 33% on one or no GDMT medications. There was not a statistically significant difference in mortality rate when comparing those with active stimulant use 5/60 (8%) to those without active illicit drug use 12/112 (11%) (RR 0.79, 95% CI, p= 0.64). 9/17 (53%) patients died of refractory cardiogenic shock, 5/17 (29%) were found in cardiopulmonary arrest of unknown etiology while undergoing treatment for acute decompensated heart failure. Two patients (12%) died of septic shock while 1/17 (5%) died of hemorrhagic shock related to chronic liver disease. Conclusion(s) The COVID-19 pandemic exacerbated significant healthcare inequalities, especially for urban underserved populations leading to late presentations of disease and worse outcomes, however, based on our data the overall inpatient mortality rate remained largely similar to pre-pandemic values.
Abstract 4145180: Prognostic value of baseline Residual Inflammatory Risk and Residual Triglyceride Risk in patients undergoing Percutaneous Coronary Intervention with optimally managed LDL Cholesterol
Authors: Francesca Di Muro, Birgit Vogel, Samantha Sartori, Benjamin Bay, ANGELO OLIVA, Mauro Gitto, Kenneth Smith, Prakash Krishnan, Joseph Sweeny, Pedro Moreno, Pier Pasquale Leone, Parasuram Krishnamoorthy, Annapoorna Kini, George Dangas, Samin Sharma, Roxana Mehran
Journal: Circulation (2024)

Background: Triglycerides (TG) denote residual triglyceride risk (RTR) while hsCRP indicates residual inflammatory risk (RIR) and both are associated with adverse cardiovascular events. Question: In patients undergoing PCI with optimally managed LDL cholesterol (LDL-C), what are the contributions of RTR and RIR to cardiovascular risk? Aim: To investigate the associations of RTR and RIR with major adverse cardiac events (MACE) in patients undergoing PCI with optimal LDL-C levels. Methods: We evaluated consecutive patients with optimal LDL-C (&lt;70 mg/dL) undergoing PCI at a large tertiary center between 2012 and 2022. Patients were categorized into four subgroups according to baseline TG and hsCRP: (i) No residual risk (hsCRP &lt;2 mg/L + TG &lt;150 mg/dL); (ii) RTR alone (hsCRP &lt;2 mg/L + TG ≥150 mg/dL); (iii) RIR alone (hsCRP &gt;2 mg/L + TG &lt;150 mg/dL); (iv) Combined RIR and RTR (hsCRP ≥2 mg/L+ TG ≥150 mg/dL). Known causes of elevated hsCRP and hsCRP &gt; 10 mg/L were exclusion criteria. The primary outcome was MACE, defined as a composite of all-cause mortality, myocardial infarction, or stroke. A Cox regression model adjusted for multiple covariates was performed to analyze outcomes using patients without residual risk as a reference. Results: A total of 9,446 patients were included in the analysis. Of these, 5,339 showed no residual risk, 3,009 RIR only, 555 RTR only, and 543 exhibited a combination of RIR and RTR. After adjustment, RIR was significantly associated with an increased risk of MACE independently of RTR (p&lt;0.001, adj. HR: 1.80, 95% CI: 1.41-2.29 for no RTR and p=0.002, adj. HR: 1.90, 95% CI: 1.27-2.86 for RTR). This was primarily driven by all-cause mortality. Conversely, in patients with only RTR, MACE and all-cause death rates were numerically higher but risk estimates were not statistically significant after adjustment ( Figure 1 ). Conclusions: Among patients undergoing PCI with optimally managed LDL-C, RIR was associated with an increased risk of MACE, while RTR did not impact outcomes. HsCRP may be used over TG to stratify the risk for adverse cardiovascular events after PCI.
Abstract 4145264: Balloon-expandable versus Self-expandable transcatheter aortic valve replacement for failed surgical prostheses: A systematic review and meta-analysis
Authors: Ahmed K. Awad, Basma Khalefa, Mazen Negmeldin Aly Yassin, Moumen Arnaout, Naydeen Mostafa, Mariana S. Naeem, Ghaith Eljadid, Syed Karam Gardezi
Journal: Circulation (2024)

Background: Transcatheter aortic valve-in-valve (VIV) replacement has emerged as a valid alternative to conventional re-operation for the treatment of failed bioprosthetic surgical aortic valves. Self-expandable valves (SEV) and balloon-expandable valves (BEV) are the two major devices used. The aim of this study is to compare outcomes between SEV and BEV when used for transcatheter aortic valve replacement (TAVR) procedures in failed surgical prostheses. &lt;div&gt; Methods: A comprehensive search was conducted on PubMed, Scopus, Web of Science, Cochrane Library, and Embase databases to identify studies comparing aortic valve in valve (ViV) with SEV and BEV for failed surgical aortic prostheses from inception to May 22, 2024. To estimate the effect size, dichotomous outcomes were pooled as risk ratio (RR), and continuous outcomes were pooled as mean difference (MD) with their respective 95% confidence interval (CI).&lt;/div&gt; &lt;div&gt; Results: We included nine studies with a total of 1258 patients in the SEV group and 1079 in the BEV group. Compared to patients in the BEV group, patients in the SEV group had significantly lower one-year mortality (RR = 0.69; 95% CI: [0.49-0.98], p = 0.04). SEV group also had less incidence of severe patient protheses mismatch (RR = 0.49; 95% CI: [0.32-0.75], p &lt;0.01). On the other hand, patients with SEV had a significantly higher risk of moderate to severe aortic regurgitation (AR) (RR = 2.71; 95% CI: [1.69-4.36], p = &lt;0.01) as well as permanent pacemaker implantation (PPI) (RR = 1.63; 95% CI: [1.18 - 2.26], p &lt;0.01). There was no difference in the rate of coronary obstruction (RR = 0.87; 95% CI: [ 0.49-1.55], p = 0.64), stroke (RR = 0.82; 95% CI: [0.42-1.58], p = 0.55), and short-term mortality (RR = 0.76; 95% CI: [0.49-1.18], p = 0.23) between both groups. One-year change in mean aortic valve gradient was comparable between both groups (MD = -13.94; 95% CI:[-31.16-3.28], p = 0.11).&lt;/div&gt; &lt;div&gt; Conclusion: The present systematic review and meta-analysis found that for patients with failed surgical protheses who underwent transcatheter aortic VIV, SEV was associated with significantly less rate of one-year mortality and severe patients Prosthesis mismatch, but higher rates of PPI implantation and AR of moderate or higher degree. These findings provide valuable information in guiding proper selection of devices for patients with degenerated aortic surgical bioprostheses. &lt;/div&gt; &lt;div&gt; &lt;/div&gt;
Abstract 4145297: Cardiac Myxomas: Presentation, Radiological Aspects, and Surgical Outcomes - Successful Results in a Series of 54 Cases
Authors: Mohammed Amine KARBI, Linda ZEBIRATE, Mohamed RAHDOUN, Sid Ahmed BENTRIKI, mhamed djezzar, Makhlouf AMIR, Mohamed OULDABDERRAHMANE, Ahmed Zaki Boukli Hacene, Sami Bouchenafa, Mohamed ATBI
Journal: Circulation (2024)

Introduction: Cardiac myxoma is a rare and benign primary cardiac tumor, accounting for 50% of all primary cardiac tumors. The aim of this study is to analyze our experience of cardiac myxomas with a significant number of cases over the past seven years. Materials and Methods: This is a retrospective and descriptive study of 54 cases of cardiac myxomas, representing 93% of all cardiac tumors surgically treated in our cardiac surgery department, from June 2017 to May 2024. All clinical, morphological, perioperative data and the possibility of recurrence and tumor embolism of these patients were analyzed. Results: The mean age of the patients was 55 ± 5 years. Women represented 65% (n=35). The circumstances of discovery were dyspnea in 57% (n=31), asymptomatic in 20% (n=11), and embolism in 15% (n=8). Auscultation was normal in 75% (n=46). Complete arrhythmia by atrial fibrillation was observed in 18.5% (n=10). Transthoracic echocardiography revealed the location of the myxoma in the left atrium in 83.3% (n=45), the right atrium in 9.3% (n=5), an exceptional location at the ventricular side of the tricuspid valve in one case, and another rare location in the left ventricle. Myxomas were obstructive in 59% (n=32). Multiple myxomas were found in 4% (n=2). They had a broad implantation base in 85% (n=46). Cardiac CT and/or MRI was used in 28% (n=15). Surgical excision under extracorporeal circulation was performed in all patients, with 18.5% (n=10) considered emergencies and 15% (n=8) performed on a beating heart. Immediate postoperative outcomes were simple in 76% (n=41). There was one death with a mortality rate of 1.8%, and two recurrences were recorded with an actuarial recurrence rate of 0.037 (95% CI: [0.000; 0.087]). The long-term prognosis was excellent with an actuarial survival rate of 0.981 (95% CI: [0.945; 1.000]). Conclusion: Myxoma is the most common benign cardiac tumor, characterized by clinical polymorphism. Transthoracic echocardiography is the reference examination. Surgery involves a wide excision of the myxoma with its implantation area and should be performed as soon as the diagnosis is confirmed to avoid any embolic complications. The prognosis after surgery is excellent, but follow-up is recommended due to the risk of recurrence.
Abstract 4145321: Association of Pulmonary Function Test Between Thrombogenicity in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention
Authors: Yong-Lee Kim, Hyounwoo Kim, HANGYUL KIM, Hye Ree Kim, Kyehwan Kim, Jeong rang Park, Jin-sin Koh, Seok-Jae Hwang, Jinyong Hwang, Min Gyu Kang
Journal: Circulation (2024)

Introduction: Pulmonary dysfunction is a risk factor for increased mortality in patients with acute coronary syndromes (ACS). The purpose of this study was to investigate the association between thrombogenicity and pulmonary function test abnormalities in patients with ACS. Methods: We included ACS patients who underwent successful percutaneous coronary intervention (PCI). Pulmonary function was assessed by spirometry based on the forced expiratory volume in one second (FEV 1 %pred) after PCI. Thrombogenicity was evaluated with the thromboelastography and conventional hemostatic measures. Results: Among 323 patients, 90 patients (28.8%) had pulmonary dysfunction (moderate or severe spirometric abnormality, FEV 1 %pred &lt;70). Patients with pulmonary dysfunction had higher levels of conventional biomarkers for thrombogenicity (D-dimer, 1.24±1.9 vs. 0.78±1.08 ug/mL, p=0.016, and fibrinogen, 383±124 vs. 331±90 mg/dL, p&lt;0.001, respectively). On thromboelastography, platelet-fibrin clot strength (PFCS) was significantly higher in patients with pulmonary dysfunction (69.2±5.9 vs. 65.4±6.7 mg/dL, p&lt;0.001). High PFCS (≥ 68 mm) was associated with pulmonary dysfunction (OR, 2.30, 95% CI 1.41 – 3.76, p=0.001). All-cause death rate for 3-years was increased in pulmonary dysfunction and high PFCS (23.3% vs. 14.1%, Log-rank test p=0.003, and 27.9% vs. 10.8%; Log-rank test p=0.003, respectively) (Fig. 1). Conclusions: This study showed the association between heightened thrombogenicity and pulmonary function test abnormalities and their prognostic implications in ACS patients. This study suggests a pathogenetic mechanism for the poor prognosis of patients with pulmonary dysfunction after PCI.
Abstract 4145256: Urban Greenspace Exposure, Stress, and Cardiovascular Function.
Authors: Cameron Stopforth, Anna Simpson, Sean Willis, Ted Smith, Aruni Bhatnagar, Rachel Keith
Journal: Circulation (2024)

Introduction: Healthy urban environments are essential for improving cardiovascular health. Although exposure to wild green surroundings has been shown to have positive effects on mental and physical health, the effect of urban greenspaces on cardiovascular function and stress remain unclear. Research Question: Does being in an urban park decrease stress and autonomic tone as reflected by heart rate variability (HRV). Methods: We invited healthy adults (n=41; age 25-70 years) to participate in a cross-over panel study. They were randomly assigned to start in either a typical urban park or an adjacent urban space, spending 20min sitting and 20min walking. Self-reported distress and State-Trait Anxiety Index (STAI) scales were assessed before and after exposure. Paired t -test was used to compare stress levels by site, and the effect size was calculated using regression analysis after adjusting for the level of starting distress. ECG recordings were acquired for the duration of the visit. HRV epochs of 5 min at the end of sitting or walking period and 40 min for the entire study were analyzed and compared using paired t -test. Results: Pre-exposure distress and STAI summed scores were similar for the park and built spaces, but the level of distress was lower after visiting the park compared with built space (19.6±15.0 vs. 24.1±12.1; p=0.05). STAI scores were decreased after visiting the park, but not the built space (-5.4±8.2 vs. 0.8±6.8; p=0.003). When adjusted for the starting levels of distress, the summed STAI score after visiting the park was reduced by 6 (-10.34, -2.11), but no change for the built site. The standard deviation of NN intervals (SDNN) was higher in the park than the urban site (41.7 vs. 37.3; p=0.03) and the HR was lower (78 vs. 81; p=0.01) across the entire study epoch (40min). There was no significant change during the seated portion of visits, but across the walking portion, the values of SDNN were higher in greenspace (32.2 vs. 27.0; p= 0.01) and HR was lower (87 vs 84; p=0.02). Other HRV indices were not significantly affected. Conclusion: Visiting an urban park, but not a built environment, led to a decrease in self-reported distress, and a relative shift in the autonomic nervous system towards parasympathetic dominance. Although the relationship between changes in stress and HRV remain unclear, access to greenspaces may be an important factor in maintaining and enhancing cardiovascular health in urban environments.
Abstract 4145277: The Utility of the Modified Shock Index (MSI) in Risk Stratification of Patients with STEMI
Authors: Jack Jnani, Spencer Weintraub, Riya George, Brandon Impastato, Maikel Kamel, Aditya Sood, Ji-Cheng Hsieh, Shreya Srivastava, Andrew Tsai, Jack Alboucai, Kishen Bulsara, Austin Cheng, Matthew Griffin, Miguel Alvarez Villela, Matthew Pierce
Journal: Circulation (2024)

Introduction: The Modified Shock Index (MSI) is easily calculated from a patient’s vital signs on admission. There have been small studies that suggest that MSI can be helpful to risk stratify patients with STEMI. Methods: We collected retrospective data on 760 patients admitted with STEMI at our quaternary academic medical center from 2018-2022. The MSI was computed as the heart rate divided by the mean arterial pressure collected on initial admission. We defined two cohorts: one with an MSI value of greater than or equal to 0.93 and one with MSI&lt;0.93 based on prior literature on the topic (Abreu et al, 2018). Vasopressors included norepinephrine, neo-synephrine, and vasopressin while inotropes included milrinone and dobutamine. We utilized multivariable logistic regression to compare our two cohorts and adjusted for collinearity. Results: In a univariate analysis, female sex (OR 1.95, 95% CI 1.32-2.87, p=0.0007), diabetes (OR 1.75, 1.21-2.54, p= 0.003), post-COVID era (OR 1.52, 1.06 to 2.21, p=0.025), and reduced ejection fraction (OR 0.98, 0.96 to 0.99, p= 0.0008) were associated with elevated MSI. In a multivariate analysis, an MSI&gt;= 0.93 was associated with over 6x increased need of vasopressors during admission (OR 6.12, 3.32-11.47, p&lt;0.0001) and almost 6x increased use of inotropes (OR 5.76, 2.54-13.44, p&lt;0.0001). An elevated MSI was also associated with 5.5x increased need for mechanical ventilation (OR 5.45, 2.91-10.41, p&lt;0.0001), 5.7x increased need for temporary mechanical circulatory support (tMCS) (OR 5.68, 3.18-10.30, p&lt;0.0001) and 2x increased risk of LV thrombus development (OR 2.23, 1.1-4.4, p= 0.02). An elevated MSI was also associated with 2.5x increased risk of CICU length of stay (LOS) &gt; 3 days (OR 2.51, 1.37-4.6, p=0.0003) and over 3x increased risk of hospital LOS greater than 1 week (OR 3.1, 1.7-5.7, p=0.0003). Conclusions: At our center, an MSI greater than or equal to 0.93 was significantly associated with the use of vasoactive agents, mechanical ventilation and tMCS. An elevated MSI was also associated with prolonged CICU and hospital LOS. MSI is a simple yet informative tool to risk stratify STEMI patients and help determine their initial level of care.
Abstract 4145247: Optimal threshold of donor-derived cell-free DNA for detection of cardiac transplant rejection: a meta-analysis
Authors: Kunal Shah, Donghee Han, In-Cheol Kim, Lily Stern, Evan Kransdorf, David Chang, Michele Hamilton, Andriana Nikolova, Michelle Kittleson, Jignesh Patel, Daniel Berman, Jon Kobashigawa
Journal: Circulation (2024)

Background: Plasma donor-derived cell-free DNA (dd-cfDNA) has emerged as a biomarker for acute heart transplant rejection as a potential adjunct to endomyocardial biopsy (EMBx). However, an established threshold for dd-cfDNA in acute cardiac transplant rejection is lacking, with prior studies employing different study specific thresholds. This meta-analysis aims to assess the overall diagnostic accuracy of dd-cfDNA across various cutoffs and provide an optimal threshold. Method: PubMed and Web of Science were searched for relevant publications reporting on the use of dd-cfDNA for the detection of acute cardiac transplant rejection defined as acute cellular rejection (ACR) and/or antibody-mediated rejection (AMR), with EMBx as the reference standard. Pooled sensitivity and specificity were estimated across different thresholds of dd-cfDNA across studies. The optimal dd-cfDNA threshold was estimated by specificity and 1-sensitivity in each data point pooled with fractional polynomial models, maximizing the Youden index between these models. Results: Out of 247 screened papers, 13 studies were included, comprising 12,017 samples from 3,723 patients. Twelve studies used both ACR and AMR and one study used only ACR for the definition of transplant rejection. The thresholds of dd-cfDNA varied across studies, ranging from 0.1 to 0.35 (Figure A). The overall pooled sensitivity and specificity for detecting acute transplant rejection were 0.68 (95% CI: 0.58-0.77) and 0.82 (95% CI: 0.74-0.88) respectively. The areas under the hierarchical modeling-based summary receiver-operating characteristics (sROC) curves were 0.82 (95% CI: 0.78-0.85). Specificity increased with higher thresholds while sensitivity decreased (Figure A and B). The optimal dd-cfDNA threshold derived from combining all included studies was 0.218. Conclusion: Dd-cfDNA assay demonstrates high diagnostic accuracy for acute cardiac transplant rejection, particularly notable for its high specificity. However, there exists significant inconsistency in dd-cfDNA thresholds across studies. Increasing the threshold leads to a trade-off between increased specificity and decreased sensitivity. A cutoff of 0.22 may be considered for dd-cfDNA screening for heart transplant rejection.