Distinct age-adjusted D-dimer threshold to rule out acute pulmonary embolism in outpatients and inpatients.

INTRODUCTION: The diagnosis of acute pulmonary embolism (PE) is combinations of clinical probability assessments, plasma D-dimer (DD) test results, and/or computed tomographic pulmonary angiography (CTPA). OBJECTIVE: The aim of this study is to explore the appropriate DD cutoff using the immunoturbidimetric method in outpatients and inpatients. METHODS: We retrospectively enrolled 2689 patients with suspected PE between January 2014 and December 2019. All patients underwent clinical probability assessments, DD tests, and CTPA. We investigated the appropriate cutoff level for plasma DD tests in the correlation analysis and receiver operating characteristic (ROC) curves. RESULTS: Among all patients, 1263 were confirmed acute PE. The age-adjusted DD level was determined to be age × 10 µg/L (for patients aged >50 years) in outpatients. This cutoff value resulted in a sensitivity of 96.75% and a specificity of 87.02%, with the area under the curve (AUC) of 0.908 and the number needed to treat (NNT) of 1.18. For inpatients, the age-adjusted cutoff values for the biomarker DD demonstrated poor specificity (13.34%) and NNT (9.88). However, when the DD cutoff was adjusted to 2 × the upper limit of normal (ULN), the sensitivity increased to 93.19%, while the specificity remained at 29.55%, with the AUC of 0.610 and the NNT of 4.76. The optimal DD cut-off value was 3010 µg/L (about 5 × ULN), resulting in a sensitivity of 75.22% and specificity of 61.72%, with the AUC of 0.727 and the NNT of 2.7. CONCLUSION: Using the immunoturbidimetric method to measure DD, an age-adjusted DD cutoff (age × 10 µg/L, if aged >50 years) should be considered for outpatients with suspected PE. For inpatients, increasing the DD cutoff value to at least 2 × ULN yields the best test performance.

Studies on Atrial Fibrillation and Venous Thromboembolism in the Past 20 Years: A Bibliometric Analysis Via CiteSpace and VOSviewer.

The conjunction of atrial fibrillation (AF) and venous thromboembolism (VTE) is common in clinical practice. Over the last 2 decades, a significant number of articles (2500) have been published about AF and VTE. To effectively analyze and present these vast amounts of information, this study uses bibliometric research methods to categorize and consolidate these publications. The number of publications has increased yearly, especially since 2012. The United States was the most prolific country, with 1054 studies published. The most productive institution was McMaster University. Gregory Y.H. Lip was the most prolific author. The keyword analysis identified that the research focuses from 2003 to 2014 were factor Xa inhibitor, dabigatran etexilate, direct thrombin inhibitor, double-blind, deep vein thrombosis, molecular weight heparin, stroke prevention, etc. From 2015 to 2016, research mainly focused on venous thromboembolism, antithrombotic therapy, anticoagulant, warfarin, atrial fibrillation, stroke, and pulmonary embolism. Studies during 2017 to 2022 focused on apixaban, direct oral anticoagulant, rivaroxaban, dabigatran, hemorrhage, edoxaban, medicine efficacy and safety, risk factors, clinical management, and vitamin K antagonists. Since 2018, novel oral anticoagulants have been the most commonly used keywords. On the whole, most studies of AF and VTE focus on pathogenesis and therapeutic drugs. The causal relationship between AF and VTE, the effectiveness and safety of novel oral anticoagulants in the treatments, the anticoagulant regimen of AF and VTE co-disease, and the treatment regimen for vulnerable populations such as the elderly or obese people were the focus of current research and will continue to be the central point of future research.

Association between triglyceride-glucose index trajectories and carotid atherosclerosis progression.

BACKGROUND: The triglyceride-glucose (TyG) index has been recognized as being an alternative cardiometabolic biomarker for insulin resistance associated with the development and prognosis of cardiovascular disease (CVD). However, the prospective relationship between baseline and long-term trajectories of the TyG index and carotid atherosclerosis (CAS) progression has yet to be investigated. METHODS: This longitudinal prospective cohort study included 10,380 adults with multiple general health checks at Peking University Third Hospital from January 2011 to December 2020. The TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). The latent class trajectory modeling method was used to analyze the TyG index trajectories over the follow-up. Based on univariate and multivariate Cox proportional hazards analyses, hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for the baseline and trajectory of the TyG index. RESULTS: During a median follow-up period of 757 days, 1813 participants developed CAS progression. Each 1-standard deviation (SD) increase in the TyG index was associated with a 7% higher risk of CAS progression after adjusting for traditional CVD risk factors (HR = 1.067, 95% CI 1.006-1.132). Similar results were observed when the TyG index was expressed as quartiles. According to different trajectory patterns, participants were categorized into low-stable, moderate-stable, and high-increasing groups. After multivariate adjustment, the moderate-stable group had a 1.139-fold (95% CI 1.021-1.272) risk of CAS progression. The high-increasing trajectory of the TyG index tended to be associated with CAS progression (HR = 1.206, 95% CI 0.961-1.513). CONCLUSIONS: Participants with higher baseline and moderate-stable trajectory of the TyG index were associated with CAS progression. Long-term trajectories of the TyG index can help to identify individuals at a higher risk of CAS progression who deserve specific preventive and therapeutic approaches.

Hamiltonian Identification via Quantum Ensemble Classification.

Identifying the Hamiltonian of an unknown quantum system is a critical task in the area of quantum information. In this article, we propose a systematic Hamiltonian identification approach via quantum ensemble multiclass classification (HI-QEMC). This approach is implemented by a three-step iterative refining process, i.e., parameter interval guess, verification, and judgment. In the parameter interval guess step, the parameter interval is divided into several sub-intervals and the true Hamiltonian parameter is guessed in one of them. In the parameter interval verification step, cross verification is applied to verify the accuracy of the guess. In the parameter interval judgment step, an adaptive interval judgment (AIJ) algorithm is designed to determine the sub-interval containing the true Hamiltonian parameter. Numerical results on two typical quantum systems, i.e., two-level quantum systems and three-level quantum systems, demonstrate the effectiveness and superior performance of the proposed approach for quantum Hamiltonian identification.

Missense mutation of SERPINC1 (p.Ser426Leu) in a young patient presenting as refractory and recurrent venous thromboembolism: A case report.

Genetic and acquired risk factors are extremely important mechanisms in the development of venous thromboembolism (VTE). Inherited antithrombin (AT) deficiency due to mutations in the SERPINC1 gene is a well-known risk factor for genetic thrombophilia. In this case, we reported a 28-year young abroad student who presented with refractory and recurrent VTE in-hospital. This patient presented with a 2-month history of right lower limb pain and 1 week of fever. The ultrasound showed deep venous thrombosis in the right common and superficial femoral veins. The CTPA confirmed acute pulmonary embolism with multiple filling defects in both pulmonary arteries. He was diagnosed with "pulmonary embolism, pneumonia, lower extremity venous thrombosis". The level of serum antithrombin was normal, yet gene sequencing revealed a heterozygous missense mutation of SERPINC1, c.1277C>T (p.Ser426Leu). The patient underwent anticoagulant therapy of heparin and inferior vena cava filter implantation. The patient had undergone recurrent VTE despite adequate anticoagulation with heparin during the first 2 weeks. The swelling, pain, and thrombosis of lower extremity veins got resolved from warfarin and rivaroxaban. Inherited antithrombin deficiency due to mutations in the SERPINC1 gene is the genetic basis of this patient, and warfarin/rivaroxaban, other than heparin, is beneficial.

Trajectories of Lipid Profile and Risk of Carotid Atherosclerosis Progression: A Longitudinal Cohort Study.

BACKGROUND: Early assessment of carotid atherosclerotic plaque characteristics is essential for atherosclerotic cardiovascular disease (ASCVD) risk stratification and prediction. We aimed to identify different trajectories of lipid profiles and investigate the association of lipid trajectories with carotid atherosclerosis (CAS) progression in a large, longitudinal cohort of the Chinese population. METHODS: 10,412 participants aged ≥18 years with ≥2 times general health checkups were included in this longitudinally prospective cohort study at Peking University Third Hospital. We used latent class trajectory models to identify trajectories of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) over follow-up time (757 days, IQR: 388-844 days). RESULTS: Participants with carotid plaque were more likely to be older, male, have higher body mass index, have a higher prevalence of hypertension and diabetes, and have a higher level of blood pressure, TG, TC, and LDL-C, compared with carotid intima-media thickness (cIMT) and normal group. Subjects were trichotomized according to different trajectory patterns into stable, moderate-stable, and elevated-increasing classes. TC ≥ 5.18 mmol/L and moderate-stable class (hazard ratio (HR): 1.416, 95% confidence interval (CI): 1.285-1.559, p: 0.000), TG ≥ 1.70 mmol/L and moderate-stable class (HR: 1.492, 95% CI: 1.163-1.913, p: 0.002), TG ≥ 1.70 mmol/L and elevated-increasing class (HR: 1.218, 95% CI: 1.094-1.357, p: 0.000), LDL-C ≥ 3.36 mmol/L and stable class (HR: 1.500, 95% CI: 1.361-1.653, p: 0.000) were statistically significant associated with CAS progression compared with the reference group. CONCLUSIONS: Borderline elevated baseline lipid (TC, TG, and LDL-C) with stable and elevated-increasing trajectories were associated with CAS progression. Long-term strategies for low-level lipid are beneficial for ASCVD management.

Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL): A Novel Biomarker for Prognostic Assessment and Risk Stratification of Acute Pulmonary Embolism.

BACKGROUND: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is associated with poor prognosis in cardiovascular diseases. However, the predictive value of TRAIL for the short-term outcome and risk stratification of acute pulmonary embolism (PE) remains unknown. METHODS: This study prospectively included 151 normotensive patients with acute PE. The study outcome was a composite of 30-day adverse events, defined as PE-related death, shock, mechanical ventilation, cardiopulmonary resuscitation, and major bleeding. RESULTS: Overall, nine of 151 (6.0%) patients experienced 30-day adverse composite events. Multivariable logistic regression showed that TRAIL was an independent predictor of study outcome (OR 0.19 per SD; 95% CI 0.04-0.90). An ROC curve revealed that TRAIL's area under the curve (AUC) was 0.83 (95% CI 0.76-0.88). The optimal cut-off value for TRAIL was 18 pg/mL, with a sensitivity, specificity, negative predictive value, positive predictive value, positive likelihood ratio, and negative likelihood ratio of 89%, 69%, 99%, 15%, 2.87, and 0.16, respectively. Compared with the risk stratification algorithm outlined in the 2019 ESC guidelines, our biomarker-based risk stratification strategy (combining TRAIL and hs-cTnI) has a similar risk classification effect. CONCLUSION: Reduced plasma TRAIL levels predict short-term adverse events in normotensive patients with acute PE. The combination of the 2019 ESC algorithm and TRAIL aids risk stratification in normotensive patients with acute PE.

Profilin 2 and Endothelial Exosomal Profilin 2 Promote Angiogenesis and Myocardial Infarction Repair in Mice.

Cardiovascular diseases (CVD) are the leading cause of death worldwide, wherein myocardial infarction (MI) is the most dangerous one. Promoting angiogenesis is a prospective strategy to alleviate MI. Our previous study indicated that profilin 2 (PFN2) may be a novel target associated with angiogenesis. Further results showed higher levels of serum PFN2 and exosomal PFN2 in patients, mice, and pigs with MI. In this study, we explored whether PFN2 and endothelial cell (EC)-derived exosomal PFN2 could increase angiogenesis and be beneficial for the treatment of MI. Serum PFN2, exosomes, and exosomal PFN2 were elevated in rats with MI. PFN2 and exosomes from PFN2-overexpressing ECs (OE-exo) enhanced EC proliferation, migration, and tube formation ability. OE-exo also significantly increased the vessel number in zebrafish and protected the ECs from inflammatory injury. Moreover, OE-exo-treated mice with MI showed improvement in motor ability, ejection fraction, left ventricular shortening fraction, and left ventricular mass, as well as increased vessel numbers in the MI location, and decreased infarction volume. Mechanistically, PI3K might be the upstream regulator of PFN2, while ERK might be the downstream regulator in the PI3K-PFN2-ERK axis. Taken together, our findings demonstrate that PFN2 and exosomal PFN2 promote EC proliferation, migration, and tube formation through the PI3K-PFN2-ERK axis. Exosomal PFN2 may be a valuable target in the repair of MI injury via angiogenesis.

Circulating Soluble Suppression of Tumorigenicity 2 Predicts Recurrence After Radiofrequency Ablation of Persistent Atrial Fibrillation.

Objective: A more extensively fibrotic left atrium contributes to atrial fibrillation (AF) occurrence, persistence, and recurrence. The soluble suppression of tumorigenicity 2 (sST2) has emerged as a ventricular fibrotic biomarker for patients with heart failure. The present study is to investigate associations between circulating sST2 and risk of recurrence after ablation in AF patients. Methods: We measured the baseline plasma level of sST2 from patients with persistent AF (n = 117) and paroxysmal AF (n = 93) patients. Patients were followed up for 15 months after ablation. The relationship between circulating sST2 and recurrence was assessed by multivariable Cox regression. The cutoff value of sST2 was determined by receiver operating characteristic curve. The relationship between baseline sST2 level and left atrial volume index (LAVI) was assessed by multivariate linear regression analysis. Serial sST2 measurements were also conducted after 24 h, 6 months, and 15 months of ablation. ST2 localization was examined in left atrial appendages of persistent AF patients by immunohistochemistry and Western blot. Results: Baseline sST2 positively associated with LAVI in the persistent AF group, and elevated sST2 (≥39.25 ng/ml) independently increased the risk of recurrence after ablation (area under the curve = 0.748), with hazard ratio of 1.038 (95% confidence interval 1.017-1.060, P < 0.001) when adjusted for co-variables. In contrast, elevated sST2 cannot predict recurrence in paroxysmal AF. Conclusions: In persistent AF patients, increased sST2 serves as a marker of recurrence after radiofrequency ablation. Patients with sST2 ≥ 39.25 ng/ml are more likely to develop recurrence within a year.

Acute myocardial infarction in twin pregnancy after assisted reproduction: A case report.

BACKGROUND: Acute myocardial infarction (AMI) during pregnancy is rare, especially in twin pregnancy, and it can endanger the lives of the mother and children. Except for conventional cardiovascular risk factors, pregnancy and assisted reproduction can increase the risk of AMI during pregnancy. AMI develops secondary to different etiologies, such as coronary spasm and spontaneous coronary artery dissection. CASE SUMMARY: A 33-year-old woman, with twin pregnancy in the 31st week of gestation, presented to the hospital with intermittent chest tightness for 12 wk, aggravation for 1 wk, and chest pain for 4 h. Combined with the electrocardiogram and hypersensitive troponin results, she was diagnosed with acute ST-elevation myocardial infarction. Although the patient had no related medical history, she presented several risk factors, such as age greater than 30 years, assisted reproduction, and hyperlipidemia. After diagnosis, the patient received antiplatelet and anticoagulant treatment. Cesarean section and coronary angiography performed 7 d later showed stenosis and thrombus shadow of the right coronary artery. After receiving medication, the patient was in good condition. CONCLUSION: This case suggests that, with the widespread use of assisted reproductive technology, more attention should be paid to perinatal healthcare, especially when chest pain occurs, to facilitate early diagnosis and intervention of AMI, and the etiology of AMI in pregnancy needs to be differentiated, especially between coronary spasm and spontaneous coronary artery dissection.

Identification of important risk factors for all-cause mortality of acquired long QT syndrome patients using random survival forests and non-negative matrix factorization.

BACKGROUND: Acquired long QT syndrome (aLQTS) is often associated with poor clinical outcomes. OBJECTIVE: The purpose of this study was to examine the important predictors of all-cause mortality of aLQTS patients by applying both random survival forest (RSF) and non-negative matrix factorization (NMF) analyses. METHODS: Clinical characteristics and manually measured electrocardiographic (ECG) parameters were initially entered into the RSF model. Subsequently, latent variables identified using NMF were entered into the RSF as additional variables. The primary outcome was all-cause mortality. RESULTS: A total of 327 aLQTS patients were included. The RSF model identified 16 predictive factors with positive variable importance values: cancer, potassium, RR interval, calcium, age, JT interval, diabetes mellitus, QRS duration, QTp interval, chronic kidney disease, QTc interval, hypertension, QT interval, female, JTc interval, and cerebral hemorrhage. Increasing the number of latent features between ECG indices, which incorporated from n = 0 to n = 4 by NMF, maximally improved the prediction ability of the RSF-NMF model (C-statistic 0.77 vs 0.89). CONCLUSION: Cancer and serum potassium and calcium levels can predict all-cause mortality of aLQTS patients, as can ECG indicators including JTc and QRS. The present RSF-NMF model significantly improved mortality prediction.

Hospitalized cancer patients with acquired long QT syndrome-a matched case-control study.

BACKGROUND: Our recent study has revealed that many hospitalized patients with acquired long QT syndrome (ALQTS) are cancer patients. This study aims to determine the risk factors and outcomes of hospitalized cancer patients with ALQTS. METHODS: We performed a matched case-control study within a cohort of 10,180 cancer patients hospitalized between September 2013 and April 2016. Among them, 150 patients defined as having severe ALQTS with a markedly prolonged QT interval (QTc ≥ 500 ms) were compared with 293 age-, sex- and cancer-type-matched controls (non-ALQTS). Death as the endpoint was followed for up to 2 years. Cox regression and Kaplan-Meier survival analyses were performed to assess the effects of particular clinical variables on all-cause mortality. Multivariate logistic regression was performed to calculate odds ratios (OR) for various predictors of QT prolongation. RESULTS: The mortality was significantly higher in ALQTS group (63.3% vs. 33.4%). Hypertension, hypokalemia, hypocalcemia, QT-prolonging drugs, infection, anemia, anti-microtubule agents were contributing factors to ALQTS. Renal insufficiency, male gender and hypokalemia were found to be independent risk factors for all-cause mortality in ALQTS group. CONCLUSION: Markedly prolonged QT interval was seen in 1.5% of hospitalized cancer patients. The all-cause mortality was high in cancer patients with severe ALQTS.

Lipocalin-2 Predicts Long-Term Outcome of Normotensive Patients with Acute Pulmonary Embolism.

Normotensive patients with acute pulmonary embolism (APE) are accompanied by heterogeneously adverse events. Responding to tissue injury, lipocalin-2 (LCN-2) is elevated in experimental APE model and associated with short-term prognosis. However, the prognostic value of LCN-2 in normotensive patients with APE for long-term major adverse events (MAEs) remains unknown. We evaluated the association of plasma LCN-2 levels with the median 467-day outcome in 170 normotensive patients with APE. We also assessed whether LCN-2 could improve risk stratification. MAEs consisted of mortality or recurrence of venous thromboembolism. During follow-up, 17 (10%) patients suffered from MAEs. These patients had higher LCN-2 levels compared with patients without MAEs (median: 13.97 vs. 8.55 ng/ml, P = 0.01). The proportion of MAEs in the intermediate-low-risk group (14.0%) was higher than that in the intermediate-high-risk group (5.3%). LCN-2 levels independently had prognostic value for MAEs in overall (HR = 3.40, 95% CI 1.46-7.90) and intermediate-risk group (HR = 3.88, 95% CI 1.63-9.23). LCN-2 also showed incremental value in overall (ΔC-index: 0.13, 95% CI 0.02-0.24; category-based NRI = 0.25, 95% CI 0.07-0.42) and intermediate-risk patients (ΔC-index: 0.13, 95% CI 0.05-0.31; category-based NRI = 0.44, 95% CI 0.24-0.65). Adding LCN-2 (cut-off value = 11 ng/ml) to the current risk algorithm improved MAEs of intermediate-risk reclassification (intermediate-high vs. intermediate-low = 25.6% vs. 6.0%, P = 0.002). Elevated plasma LCN-2 levels predict long-term MAEs among normotensive patients with APE. LCN-2 might be a useful biomarker for risk stratification in the intermediate-risk group.

Higher High-Sensitivity C Reactive Protein is Associated with Future Premature Ventricular Contraction: a Community Based Prospective Cohort Study.

We aimed to determine whether hs-CRP is a predictor of future premature ventricular contraction (PVC) events in a community based population. A total of 101,510 participants were recruited at baseline (2006-2007). The follow-up visits were conducted every two years. Participants who were free from PVC at baseline and achieved the fourth visit, or diagnosed of PVC during the subsequent visits were included for analyses. Diagnosis of PVC was based on standard supine resting, 10-s 12-lead ECG. Cox regression was applied to evaluate the association between quartiles of hs-CRP and the incidence of PVCs. 60710 participants (male: 79.9%, mean age 49.4 years) were included for analyses. During a mean follow-up of 74.9 ± 7.4 months, 908 (1.5%) participants were diagnosed with PVC. Participants of the highest quartile of hs-CRP had significantly increased risk of PVC events as compared with the lowest quartile (HR 1.36; 95% CI 1.12-1.66); and stratified analyses showed similar result in males (HR 1.45; 95% CI 1.16-1.80), but not in females (HR 1.12; 95% CI 0.71-1.79). Moreover, elevated serum hs-CRP was associated with future PVC in participants without history of myocardial infarction or stroke (HR 1.34; 95% CI 1.09-1.65). Elevated hs-CRP was an independent predictor of PVC in Chinese population, especially in men.

Acquired long QT syndrome in hospitalized patients.

BACKGROUND: Acquired long QT syndrome (ALQTS) has long been overlooked in clinical practice. Recent studies reported that severe ALQTS (QTc ≥500 ms) in hospitalized patients is associated with increased all-cause mortality. OBJECTIVE: The purpose of this study was to determine the role of ALQTS in the clinical outcomes of hospitalized patients. METHODS: Electronic medical records were reviewed to identify severe ALQTS in hospitalized patients in a single study center from September 1, 2013, to February 28, 2014. Up to 1-year follow-up was conducted in the ALQTS subjects and compared with age-, gender-, and admitting diagnosis-matched hospitalized patients with a normal QT interval. RESULTS: Severe ALQTS (QTc 529 ± 38 ms) was seen in 0.7% (293/41,649) of hospitalized patients, of whom 86% were treated in noncardiology departments. All-cause mortality was 32% in the ALQTS group vs 14% in the control group (P <.001) during follow-up of 255 ± 63 days. Syncope and life-threatening ventricular arrhythmia were more frequent in patients with severe ALQTS (6% vs 0.6%, P <.0001). Cerebral hemorrhage (odds ratio [OR] 6.405, 95% confidence interval [CI] 2.341-17.525), cancer (OR 5.937, 95% CI 2.658-13.260), infection (OR 2.207, 95% CI 1.124-4.333), and end-stage disease (OR 2.092, 95% CI 1.045-4.191) are the major contributors to all-cause mortality in ALQTS. CONCLUSION: Severe ALQTS is not uncommon in hospitalized patients. It can be easily overlooked because the majority of patients with severe ALQTS are treated in noncardiology departments. The clinical outcome of severe ALQTS is poor. Removing QT-prolonging factors may reduce the risks of fatal arrhythmia and sudden death in patients with ALQTS.