Natural Language Processing in a Clinical Decision Support System for the Identification of Venous Thromboembolism: Algorithm Development and Validation.

BACKGROUND: It remains unknown whether capturing data from electronic health records (EHRs) using natural language processing (NLP) can improve venous thromboembolism (VTE) detection in different clinical settings. OBJECTIVE: The aim of this study was to validate the NLP algorithm in a clinical decision support system for VTE risk assessment and integrated care (DeVTEcare) to identify VTEs from EHRs. METHODS: All inpatients aged ≥18 years in the Sixth Medical Center of the Chinese People's Liberation Army General Hospital from January 1 to December 31, 2021, were included as the validation cohort. The sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-, respectively), area under the receiver operating characteristic curve (AUC), and F1-scores along with their 95% CIs were used to analyze the performance of the NLP tool, with manual review of medical records as the reference standard for detecting deep vein thrombosis (DVT) and pulmonary embolism (PE). The primary end point was the performance of the NLP approach embedded into the EHR for VTE identification. The secondary end points were the performances to identify VTE among different hospital departments with different VTE risks. Subgroup analyses were performed among age, sex, and the study season. RESULTS: Among 30,152 patients (median age 56 [IQR 41-67] years; 14,247/30,152, 47.3% females), the prevalence of VTE, PE, and DVT was 2.1% (626/30,152), 0.6% (177/30,152), and 1.8% (532/30,152), respectively. The sensitivity, specificity, LR+, LR-, AUC, and F1-score of NLP-facilitated VTE detection were 89.9% (95% CI 87.3%-92.2%), 99.8% (95% CI 99.8%-99.9%), 483 (95% CI 370-629), 0.10 (95% CI 0.08-0.13), 0.95 (95% CI 0.94-0.96), and 0.90 (95% CI 0.90-0.91), respectively. Among departments of surgery, internal medicine, and intensive care units, the highest specificity (100% vs 99.7% vs 98.8%, respectively), LR+ (3202 vs 321 vs 77, respectively), and F1-score (0.95 vs 0.89 vs 0.92, respectively) were in the surgery department (all P<.001). Among low, intermediate, and high VTE risks in hospital departments, the low-risk department had the highest AUC (1.00 vs 0.94 vs 0.96, respectively) and F1-score (0.97 vs 0.90 vs 0.90, respectively) as well as the lowest LR- (0.00 vs 0.13 vs 0.08, respectively) (DeLong test for AUC; all P<.001). Subgroup analysis of the age, sex, and season demonstrated consistently good performance of VTE detection with >87% sensitivity and specificity and >89% AUC and F1-score. The NLP algorithm performed better among patients aged ≤65 years than among those aged >65 years (F1-score 0.93 vs 0.89, respectively; P<.001). CONCLUSIONS: The NLP algorithm in our DeVTEcare identified VTE well across different clinical settings, especially in patients in surgery units, departments with low-risk VTE, and patients aged ≤65 years. This algorithm can help to inform accurate in-hospital VTE rates and enhance risk-classified VTE integrated care in future research.

Correction: Vital Signs During the COVID-19 Outbreak: A Retrospective Analysis of 19,960 Participants in Wuhan and Four Nearby Capital Cities in China.

[This corrects the article DOI: 10.5334/gh.913.].

Vital Signs During the COVID-19 Outbreak: A Retrospective Analysis of 19,960 Participants in Wuhan and Four Nearby Capital Cities in China.

Background: The implications of city lockdown on vital signs during the COVID-19 outbreak are unknown. Objective: We longitudinally tracked vital signs using data from wearable sensors and determined associations with anxiety and depression. Methods: We selected all participants in the HUAWEI Heart Study from Wuhan and four nearby large provincial capital cities (Guangzhou, Chongqing, Hangzhou, Zhengzhou) and extracted all data from 26 December 2019 (one month before city lockdown) to 21 February 2020. Sleep duration and quality, daily steps, oxygen saturation and heart rate were collected on a daily basis. We compared the vital signs before and after the lockdown using segmented regression analysis of the interrupted time series. The depression and anxiety cases were defined as scores ≥8 on the Hospital Anxiety and Depression Scale depression and anxiety subscales [HADS-D and HADS-A] in 727 participants who finished the survey. Results: We included 19,960 participants (mean age 36 yrs, 90% men). Compared with pre-lockdown, resting heart rate dropped immediately by 1.1 bpm after city lockdown (95% confidence interval [CI]: -1.8, -0.4). Sleep duration increased by 0.5 hour (95% CI: 0.3, 0.8) but deep sleep ratio decreased by 0.9% (95% CI: -1.2, -0.6). Daily steps decreased by 3352 steps (95% CI: -4333, -2370). Anxiety and depression existed in 26% and 17% among 727 available participants, respectively, and associated with longer sleep duration (0.2 and 0.1 hour, both p < 0.001). Conclusions: Lockdown of Wuhan in China was associated with an adverse vital signs profile (reduced physical activity, heart rate, and sleep quality, but increased sleep duration). Wearable devices in combination with mobile-based apps may be useful to monitor both physical and mental health. Clinical trial registration: The trial is registered at Chinese Clinical Trial Registry (ChiCTR) website (ChiCTR-OOC-17014138).

Application of cardiac computed tomographic imaging and fluoroscopy fusion for guiding left atrial appendage occlusion.

OBJECTIVE: Evaluate the value of 3D computed tomography (CT) and CT-integrating fluoroscopy for procedural guidance during WATCHMAN implantation. METHODS: This observational study compared the clinical and procedural parameters for LAAO with and without fusion imaging. Forty-one pairs of patients-matched by procedure month and with or without the use of the image fusion system-were enrolled. Using the image fusion Advanced Workstation 4.6 software (GE Healthcare), we identified the 3D cardiac anatomy and safe zones for septal punch. The LAA orifice anatomy outlines were then projected onto the real-time fluoroscopy image during the procedure to guide all the steps of LAAO. RESULTS: The use of image fusion significantly reduced the procedural time, compared to the time required for the control group (44.73 ± 20.03 min vs. 63.73 ± 26.10 min, respectively; P < 0.001). When compared to the standard procedure, the use of image fusion significantly reduced both the total radiation dose (448.80 ± 556.35 mGy vs. 798.42 ± 616.34 mGy; P = 0.004) and dose area product (DAP) (38.03 ± 47.15 Gy∙cm2 vs. 67.66 ± 52.23 Gy∙cm2, P = 0.004). Corresponding to the radiation dose, the contrast volume was also reduced (67.32 ± 18.65 vs. 90.98 ± 25.03 ml; P = 0.0004). During short-term follow-up at 6 months, there was only one femoral hematoma and incomplete LAA sealing (>3 mm) in either group. CONCLUSIONS: Automated real-time integration of cardiac CT and fluoroscopy is feasible, safe, and applicable in LAAO. It may significantly reduce the radiation exposure, procedure duration, and volume of contrast media. Following these results, the potential of merging reconstructed 3D CT scans with real-time coronary angiography should be fully exploited in LAAO.

Validation of Single Centre Pre-Mobile Atrial Fibrillation Apps for Continuous Monitoring of Atrial Fibrillation in a Real-World Setting: Pilot Cohort Study.

BACKGROUND: Atrial fibrillation is the most common recurrent arrhythmia in clinical practice, with most clinical events occurring outside the hospital. Low detection and nonadherence to guidelines are the primary obstacles to atrial fibrillation management. Photoplethysmography is a novel technology developed for atrial fibrillation screening. However, there has been limited validation of photoplethysmography-based smart devices for the detection of atrial fibrillation and its underlying clinical factors impacting detection. OBJECTIVE: This study aimed to explore the feasibility of photoplethysmography-based smart devices for the detection of atrial fibrillation in real-world settings. METHODS: Subjects aged ≥18 years (n=361) were recruited from September 14 to October 16, 2018, for screening of atrial fibrillation with active measurement, initiated by the users, using photoplethysmography-based smart wearable devices (ie, a smart band or smart watches). Of these, 200 subjects were also automatically and periodically monitored for 14 days with a smart band. The baseline diagnosis of "suspected" atrial fibrillation was confirmed by electrocardiogram and physical examination. The sensitivity and accuracy of photoplethysmography-based smart devices for monitoring atrial fibrillation were evaluated. RESULTS: A total of 2353 active measurement signals and 23,864 periodic measurement signals were recorded. Eleven subjects were confirmed to have persistent atrial fibrillation, and 20 were confirmed to have paroxysmal atrial fibrillation. Smart devices demonstrated >91% predictive ability for atrial fibrillation. The sensitivity and specificity of devices in detecting atrial fibrillation among active recording of the 361 subjects were 100% and about 99%, respectively. For subjects with persistent atrial fibrillation, 127 (97.0%) active measurements and 2240 (99.2%) periodic measurements were identified as atrial fibrillation by the algorithm. For subjects with paroxysmal atrial fibrillation, 36 (17%) active measurements and 717 (19.8%) periodic measurements were identified as atrial fibrillation by the algorithm. All persistent atrial fibrillation cases could be detected as "atrial fibrillation episodes" by the photoplethysmography algorithm on the first monitoring day, while 14 (70%) patients with paroxysmal atrial fibrillation demonstrated "atrial fibrillation episodes" within the first 6 days. The average time to detect paroxysmal atrial fibrillation was 2 days (interquartile range: 1.25-5.75) by active measurement and 1 day (interquartile range: 1.00-2.00) by periodic measurement (P=.10). The first detection time of atrial fibrillation burden of <50% per 24 hours was 4 days by active measurement and 2 days by periodic measurementThe first detection time of atrial fibrillation burden of >50% per 24 hours was 1 day for both active and periodic measurements (active measurement: P=.02, periodic measurement: P=.03). CONCLUSIONS: Photoplethysmography-based smart devices demonstrated good atrial fibrillation predictive ability in both active and periodic measurements. However, atrial fibrillation type could impact detection, resulting in increased monitoring time. TRIAL REGISTRATION: Chinese Clinical Trial Registry of the International Clinical Trials Registry Platform of the World Health Organization ChiCTR-OOC-17014138; http://www.chictr.org.cn/showprojen.aspx?proj=24191.

Diagnostic Performance of a Smart Device With Photoplethysmography Technology for Atrial Fibrillation Detection: Pilot Study (Pre-mAFA II Registry).

BACKGROUND: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. The asymptomatic nature and paroxysmal frequency of AF lead to suboptimal early detection. A novel technology, photoplethysmography (PPG), has been developed for AF screening. However, there has been limited validation of mobile phone and smart band apps with PPG compared to 12-lead electrocardiograms (ECG). OBJECTIVE: We investigated the feasibility and accuracy of a mobile phone and smart band for AF detection using pulse data measured by PPG. METHODS: A total of 112 consecutive inpatients were recruited from the Chinese PLA General Hospital from March 15 to April 1, 2018. Participants were simultaneously tested with mobile phones (HUAWEI Mate 9, HUAWEI Honor 7X), smart bands (HUAWEI Band 2), and 12-lead ECG for 3 minutes. RESULTS: In all, 108 patients (56 with normal sinus rhythm, 52 with persistent AF) were enrolled in the final analysis after excluding four patients with unclear cardiac rhythms. The corresponding sensitivity and specificity of the smart band PPG were 95.36% (95% CI 92.00%-97.40%) and 99.70% (95% CI 98.08%-99.98%), respectively. The positive predictive value of the smart band PPG was 99.63% (95% CI 97.61%-99.98%), the negative predictive value was 96.24% (95% CI 93.50%-97.90%), and the accuracy was 97.72% (95% CI 96.11%-98.70%). Moreover, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of mobile phones with PPG for AF detection were over 94%. There was no significant difference after further statistical analysis of the results from the different smart devices compared with the gold-standard ECG (P>.99). CONCLUSIONS: The algorithm based on mobile phones and smart bands with PPG demonstrated good performance in detecting AF and may represent a convenient tool for AF detection in at-risk individuals, allowing widespread screening of AF in the population. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-OOC-17014138; http://www.chictr.org.cn/showproj.aspx?proj=24191 (Archived by WebCite at http://www.webcitation/76WXknvE6).

A Simple Clinical Risk Score (C2HEST) for Predicting Incident Atrial Fibrillation in Asian Subjects: Derivation in 471,446 Chinese Subjects, With Internal Validation and External Application in 451,199 Korean Subjects.

BACKGROUND: The incidence of atrial fibrillation (AF) is increasing, conferring a major health-care issue in Asia. No risk score for predicting incident AF has been specifically developed in Asian subjects. Our aim was to investigate risk factors for incident AF in Asian subjects and to combine them into a simple clinical risk score. METHODS: Risk factors for incident AF were analyzed in 471,446 subjects from the Chinese Yunnan Insurance Database (internal derivation cohort) and then combined into a simple clinical risk score. External application of the new score was performed in 451,199 subjects from the Korean National Health Insurance Service (external cohort). RESULTS: In the internal cohort, structural heart disease (SHD), heart failure (HF), age ≥ 75 years, coronary artery disease (CAD), hyperthyroidism, COPD, and hypertension were associated with incident AF. Given the low prevalence and the strong association of SHD with incident AF (hazard ratio, 26.07; 95% CI, 18.22-37.30; P < .001), these patients should be independently considered as high risk for AF and were excluded from the analysis. The remaining predictors were combined into the new simple C2HEST score: C2: CAD/COPD (1 point each); H: hypertension (1 point); E: elderly (age ≥ 75 years, 2 points); S: systolic HF (2 points); and T: thyroid disease (hyperthyroidism, 1 point). The C2HEST score showed good discrimination with the area under the curve (AUC) of 0.75 (95% CI, 0.73-0.77) and had good calibration (P = .774). The score was internally validated by bootstrap sampling procedure, giving an AUC of 0.75 (95% CI, 0.73-0.77). External application gave an AUC of 0.65 (95% CI, 0.65-0.66). The C2HEST score was superior to CHADS2 and CHA2DS2-VASc scores in both cohorts in predicting incident AF. CONCLUSIONS: We have developed and validated the C2HEST score as a simple clinical tool to assess the individual risk of developing AF in the Asian population without SHD.

A risk prediction score model for predicting occurrence of post-PCI vasovagal reflex syndrome: a single center study in Chinese population.

BACKGROUND: The vasovagal reflex syndrome (VVRS) is common in the patients undergoing percutaneous coronary intervention (PCI). However, prediction and prevention of the risk for the VVRS have not been completely fulfilled. This study was conducted to develop a Risk Prediction Score Model to identify the determinants of VVRS in a large Chinese population cohort receiving PCI. METHODS: From the hospital electronic medical database, we identified 3550 patients who received PCI (78.0% males, mean age 60 years) in Chinese PLA General Hospital from January 1, 2000 to August 30, 2016. The multivariate analysis and receiver operating characteristic (ROC) analysis were performed. RESULTS: The adverse events of VVRS in the patients were significantly increased after PCI procedure than before the operation (all P< 0.001). The rate of VVRS [95% confidence interval (CI)] in patients receiving PCI was 4.5% (4.1%-5.6%). Compared to the patients suffering no VVRS, incidence of VVRS involved the following factors, namely female gender, primary PCI, hypertension, over two stents implantation in the left anterior descending (LAD), and the femoral puncture site. The multivariate analysis suggested that they were independent risk factors for predicting the incidence of VVRS (all P < 0.001). We developed a risk prediction score model for VVRS. ROC analysis showed that the risk prediction score model was effectively predictive of the incidence of VVRS in patients receiving PCI (c-statistic 0.76, 95% CI: 0.72-0.79, P < 0.001). There were decreased events of VVRS in the patients receiving PCI whose diastolic blood pressure dropped by more than 30 mmHg and heart rate reduced by 10 times per minute (AUC: 0.84, 95% CI: 0.81-0.87, P < 0.001). CONCLUSION: The risk prediction score is quite efficient in predicting the incidence of VVRS in patients receiving PCI. In which, the following factors may be involved, the femoral puncture site, female gender, hypertension, primary PCI, and over 2 stents implanted in LAD.

Prognostic factors of clinical endpoints in elderly patients with atrial fibrillation during a 2-year follow-up in China: An observational cohort study.

This study aimed to reveal the incidence of clinical endpoints in elderly patients with atrial fibrillation (AF) during a 2-year follow-up and evaluate the related prognostic factors of these endpoints.In total, 200 elderly patients with AF and 400 age- and sex-matched patients without AF were enrolled in this prospective observational cohort study. The incidence of clinical endpoints, including thromboembolism, hemorrhage, and all-cause death, during the 2-year follow-up was analyzed. Other follow-up data, including disease history, laboratory examinations, medication status, and other clinical endpoints, were collected. The prognostic factors of these clinical endpoints were then evaluated by Cox-survival analysis. In addition, the predicative role of C-reactive protein (CRP) and platelet-activating factor (PAF) on these clinical endpoints was analyzed.The incidence of clinical endpoints, including thromboembolism, hemorrhage, and all-cause death, was significantly higher in patients with AF than in those without AF (27.8% vs 9.8%, 29.4% vs 12.7%, and 28.7% vs 11.6%, respectively; all P < .001). Antithrombotic therapy significantly reduced the incidences of all-cause deaths (P < .05). Body mass index (BMI) and digoxin were prognostic risk factors of thromboembolism; age, massive hemorrhage history, and digoxin were prognostic risk factors of hemorrhage and age, renal insufficiency history, massive hemorrhage history, and digoxin were prognostic risk factors of all-cause death (P < .05). Further, both CRP and PAF were prognostic risk factors of thromboembolism and massive hemorrhage (P < .05).Age, BMI, massive hemorrhage history, and digoxin appear to be prognostic risk factors of clinical endpoints in elderly patients with AF. Appropriate drug use during follow-up may be beneficial in preventing the occurrence of clinical endpoints in elderly patients with AF. TRIAL REGISTRATION NUMBER: ChiCTR-OCH-13003479.

[Management of antithrombotic agents for endoscopic procedures in elderly Chinese patients: a retrospective study].

OBJECTIVE: To investigate the peri-endoscopic management of antithrombotic drugs and adverse events in elderly patients un-dergoing gastrointestinal endoscopy in order to provide clinical guidance of peri-endoscopic management of antithrombotic drugs for elderly pa-tients. METHODS: Between January 1st 2008 and December 31st 2014, clinical data of 3 747 patients (aged 46~99 years, 96.1% male) who were hospitalized for elective gastrointestinal endoscopy were analyzed retrospectively. The general clinical data, cardiovascular disease and re-lated risk factors, medication, management of peri-endoscopic antithrombotics and adverse events were recorded. The differences of peri-endo-scopic adverse events including thromboembolism and bleeding between patients with different management strategies of peri-endoscopic an-tithrombotics were analyzed. RESULTS: The overall incidences of peri-endoscopic thromboembolism and bleeding were 2.24% and 1.89%, re-spectively. The incidences of thromboembolism and bleeding when stopping antithrombotics at 0~7 days pre-procedure were 1.87% and 2.38% respectively. The incidences of thromboembolism and bleeding when resuming antithrombotics at 2~7 days after endoscopy were 2.07% and 0.63% respectively. When discontinuing antithrombotics, the differences in peri-endoscopic thromboembolism and bleding be-tween patients who did and did not undergo low-molecular-weight heparin (LMWH) bridging therapy were not significant. The incidence of bleeding in patients who underwent LMWH bridging therapy was higher than that in patients who didn't undergo LMWH bridging therapy, but the diference was not significant. CONCLUSIONS: Our findings suggest that cessation of antithrombotics < 7 days pre-procedures and resumption of antithrombotic agents after 2-7 days post-porcedures is optimal in elderly Chinese patients undergoing endoscopy.

Assessing bleeding risk in 4824 Asian patients with atrial fibrillation: The Beijing PLA Hospital Atrial Fibrillation Project.

The risks of major bleeding and intracranial hemorrhage (ICH) are higher in Asian patients with atrial fibrillation (AF) compared to non-Asians. We aimed to investigate risk factors for bleeding, and validate the predictive value of available bleeding risk scores (mOBRI, HEMORR2HAGES, Shireman, HAS-BLED, ATRIA and ORBIT) in a large cohort of Chinese inpatients with AF. Using hospital electronic medical databases, we identified 4824 AF patients (mean age 67 years; 34.9% female) from January 1, 1995 to May 30, 2015, with median (interquartile) in-hospital days of 10 (7-16) days. On multivariate analysis, prior bleeds, vascular disease, anemia, prior stroke, and liver dysfunction were independent risk factors of major bleeding (all p < 0.05). C-statistics (95%CI) of the HAS-BLED score were 0.72 (0.65-0.79) for major bleeding events and 0.83 (0.75-0.91) for ICH (all p < 0.001). Compared to other risk scores, the HAS-BLED score was significantly better in predicting major bleeding events (Delong test, all P < 0.05, apart from mOBRI, HEMORR2HAGES) and ICH (all p < 0.05), and additionally, resulted in a net reclassification improvement (NRI) of 17.1-65.5% in predicting major bleeding events and 29.5-67.3% in predicting ICH (all p < 0.05). We conclude that the HAS-BLED score had the best predictive and discriminatory ability for major bleeding and ICH in an Asian/Chinese AF population.

Long-term outcomes of high-risk elderly male patients with multivessel coronary disease: optimal medical therapy versus revascularization.

BACKGROUND: Many studies have indicated that medical therapy and percutaneous coronary intervention have similar effects in terms of the long-term prognosis of patients with stable coronary artery disease. This study investigated the effects of optimal medical therapy (OMT) and revascularization-plus-OMT in elderly patients with high-risk angina. METHODS: In this prospective non-randomized study, 241 consecutive high-risk elderly male patients (65-92 years of age) with angiographically confirmed multivessel disease were enrolled in the registry from January 2004 to April 2005. Of these, 98 patients underwent OMT and 143 underwent revascularization therapy plus OMT. RESULTS: After 6.5 years of follow-up, we found that the rate of long-term cardiac mortality was significantly higher in patients who underwent OMT than in those who underwent revascularization (6.5-year unadjusted mortality rate, 14.3% for OMT vs. 7.0% for revascularization patients; log-rank P = 0.04). However, the overall risks of major adverse cardiac cerebrovascular events (MACCE) were similar among all patients (6.5-year unadjusted mortality rate, 29.6% for OMT vs. 27.3% for revascularization patients; log-rank P = 0.67). CONCLUSIONS: OMT was associated with an increase in cardiac death but a similar 6.5-year risk of MACCE compared with revascularization in high-risk elderly male patients with coronary multivessel disease.

Effects of body mass index on risks for ischemic stroke, thromboembolism, and mortality in Chinese atrial fibrillation patients: a single-center experience.

BACKGROUND: Obesity is considered to be related to recurrence of atrial fibrillation (AF), left atrial thrombus formation, and atrial remodeling. However, whether obesity is an independent risk factor for stroke and other thromboembolic events is still controversial. OBJECTIVE: This study aimed to investigate the effects of body mass index (BMI) on the risks of stroke, thromboembolism, and mortality in AF patients. METHODS: Patients who were diagnosed with nonvalvular AF were included in this observational, retrospective study. The study population was stratified by BMI at baseline. The Cox proportional hazard model was adopted to calculate adjusted hazard ratios of risk factors for adverse clinical events (stroke, thromboembolism, and mortality). RESULTS: A total of 1286 AF patients (males, 78.30%; mean age, 74.50 years; 94.48% paroxysmal AF) were followed up for a median of 2.1 years (IQR: 1.5-2.9 years). Overall, 159 patients died. A total of 84 strokes and 35 thromboembolic events occurred. Multivariate analysis showed that overweight (25.0≤BMI<30.0 kg/m2) and age ≥75 years were independent risk factors for ischemic stroke (both P<0.01). Obesity (BMI ≥30.0 kg/m2), age ≥75 years, persistent/permanent AF, and prior thromboembolism were independent risk factors for thromboembolism (all P<0.05). Underweight (BMI <18.5 kg/m2), age ≥75 years, prior ischemic stroke/transient ischemic attack, renal dysfunction, and heart failure were independent risk factors for all-cause deaths (all P<0.05). CONCLUSIONS: Overweight or obesity may be a risk factor of ischemic stroke and thromboembolism in AF patients. Excessive low weight is significantly associated with increased all-cause mortality.

Resistin might not be a risk factor for carotid artery atherosclerosis in elderly Chinese males.

OBJECTIVE: To investigate the correlation between the serum resistin level and carotid artery atherosclerosis in elderly Chinese males. METHODS: The study enrolled 235 elderly Chinese males [median age 76 (range 60-97) years] scheduled for ultrasound examination of carotid artery plaque and determination of carotid artery intima-media thickness (CIMT). They were divided into carotid atherosclerotic plaque (CAP) and carotid atherosclerotic plaque-free (CAP-free) groups according to the ultrasound results. Their clinical profiles were collected, and the serum resistin and other blood biochemistry levels were determined. RESULTS: The CAP group was older and had a thicker mean CIMT than the CAP-free group. However, there was no difference in the serum resistin level between the groups. CIMT was positively correlated with age (r = 0.299, P < 0.001). The serum resistin level was not correlated with CIMT, even after controlling for age. Multiple linear regression analysis revealed that age (ß = 0.001, P < 0.001) and body mass index (ß = 0.002, P = 0.015) were significantly and positively correlated with the mean CIMT. Only age [odds ratio (OR): 1.159; 95% confidence interval (CI): 1.078-1.183, P < 0.001] was associated with the presence of carotid artery atherosclerotic plaque. The serum resistin level was not correlated with the mean CIMT or associated with the presence of carotid artery atherosclerotic plaque. CONCLUSION: The results suggest that resistin might not be a risk factor for atherosclerosis in elderly Chinese males.

[Clinical features and risk factors of stroke/thromboembolism and bleeding in the elderly patients with atrial fibrillation].

OBJECTIVE: The relationship between stroke/thromboembolic events (TEs) and bleeding as well as age-related risk factors are not fully clear in elderly patients with atrial fibrillation (AF). This study aimed to evaluate the clinical features, incidence and risk factors of stroke and bleeding in elderly AF patients. METHOD: A total of 220 elderly AF patients [mean age (83.1 ± 0.6) years] were followed for (3.2 ± 0.8) years. The CHA(2)DS(2)-VASc score, the HAS-BLED score, annual major bleeding risk and the annual stroke were analyzed. RESULT: The CHA(2)DS(2)-VASc score in patients with 65-79, 80-89 and ≥ 90 years old groups were 2.9 ± 0.2, 5.2 ± 0.2 and 5.6 ± 0.2, respectively (P < 0.001) and the HAS-BLED score were 2.1 ± 0.1, 3.2 ± 0.1 and 3.6 ± 0.1, respectively (P < 0.001), both significantly increased with aging. The annual major bleeding risk increased similarly as the annual stroke risk in the very elderly AF patients (patients 80-89 years old: bleeding risk 3.7 %, stroke risk 6.7 %; patients ≥ 90 years old: 8.7 % and 9.8 %, respectively). The combination of CHA(2)DS(2)-VASc and HAS-BLED could identify those patients with high risk for stroke and bleeding correctly. Twelve (5.5%) patients experienced "bidirectional events" (concomitant TE and haemorrhage), of whom 9 (75.0 %) suffered recurrent TEs. CONCLUSION: The bleeding risk increased similarly as the thromboembotic risk with increasing age in the elderly AF patients, "bidirectional events" is not common but related with worse outcome in elderly AF patients.

[Treatment of chronic heart failure by overexpressing sarcoplasmic reticulum calcium ATPase through gene therapy: an experiment with rats].

OBJECTIVE: To evaluate the value of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) in the gene therapy of congestive heart failure. METHODS: (1) The abdominal aortas of 51 male SD rats were isolated and ligated so as to establish models of heart failure caused by contraction of abdominal aortas. 20 rats undergoing isolation of the abdominal aorta without ligation were used as controls. 18 approximately 20 days after the operation heart failure occurred, then the rats with contraction of abdominal aorta and heart failure were randomly divided into 3 groups: rAAV-SERCA2a group (recombinant adeno-associated virus containing SERCA2a cDNA, rAAV-SERCA2a, of the concentration of 2 x 10(11) v.g was injected via diaphragm into the pericardia cavity), heart failure control group (without trentment) and rAAV2-EGFP group (the control virus rAAV2-EGFP of the concentration of 2 x 10(11) v.g was injected via diaphragm into the pericardial cavity). 10 and 30 days after virus injection, a catheter was inserted through the jugular vein into the left ventricle to record the left ventricle systole pressure (LVSP), left ventricle end diastole pressure (LVEDP), left ventricle pressure maximum increase speed (+dp/dt), and left ventricle pressure maximum decrease speed (-dp/dt), and heart rate (HR). Then all the rats were killed and their hearts were taken out to examine the expression of the SERCA2a protein. (2) The left coronary arteries of 25 male SD rats were ligated so as to establish the models of cardiac infarction. 9 rats underwent isolation of the left coronary arteries without ligation and were used as controls. Four weeks after the operation thoracotomy was performed on the rats with heart failure caused by heart infarction, rAV-SERCA2a or rAV2-EGFP were injected into the myocardium, and dilute solution was injected to the control rats. 21 days later all the rats were performed hemodynamic exams. RESULTS: (1) Thirty days after the transfection the LVSP, +dp/dt, and -dp/dt of the rAAV-SERCA2a group were significantly higher than those of the rAAV2-EGFP group by 57% (94 mm Hg vs 147 mm Hg), 110% (5350 mm Hg/s vs 11 225 mm Hg/s), and 99.8% (4198 mm Hg/s vs 8390 mm Hg/s) respectively, meanwhile the LVEDP was significantly lower by 60% (22 mm Hg vs 9 mm Hg). These homodynamic parameters of the rAAV-SERCA2a group were not significantly different from those of the control group. Thirty days after transfection the expression of SERCA2a protein of the SERCA2a group was significantly higher than those of the control heart failure and rAAV2-EGFP groups. (2) Twenty-one days after the transfection, the LVSP, +dp/dt, and -dp/dt of the SERCA2a group were significantly higher than those of the control group by 28% (86 mm Hg vs 110 mm Hg), 41% (4272 mm Hg/s vs 6026 mm Hg/s), and 71% (2789 mm Hg/s vs 4756 mm Hg/s) respectively, and the LVEDP was significantly lower by 70% (3.89 mm Hg vs -5.34 mm Hg), however, these homodynamic parameters of the rAV-SERCA2a group were all worse compared with the control false operation group. CONCLUSION: The recombinant viruses, rAAV-SERCA2a and rAV-SERCA2a, effectively deliver the SERCA2a gene and improve the homodynamic state.

[Bone marrow stem cells-based SERCA2a gene therapy for heart failure after acute myocardium infarction].

OBJECTIVE: Explore the possibility of MSC to be used to target delivery of therapeutic gene and evaluate the therapeutic effects among gene therapy, MSC transplantation and MSC-based gene therapy. METHODS: MSC were infected with an adenoviral expression vector carrying SERCA2a. SD female rats were used to make animal model with heart failure after AMI and divided into 4 groups randomly. Group I (n = 7) received SERCA2a gene therapy, group II (n = 7) received MSC transplantation, group III (n = 8) received MSC infected with SERCA2a gene transplantation, and group IV (n = 7) received empty adenoviral vector. Cardiac function was evaluated by echocardiography and physiological recorder. SERCA2a gene and protein expression were evaluated by RT-PCR and Western blot respectively. RESULTS: Compared to group IV, EF and FS of group I, group II and group III were elevated significantly on 14 days after therapy (EF: 67.7 +/- 3.9, 62.6 +/- 4.0, 67.9 +/- 3.7 versus 45.0 +/- 2.2; FS: 33.9 +/- 1.9, 31.1 +/- 2.0, 33.9 +/- 1.9 versus 22.5 +/- 1.1, P < 0.05). While the elevation values of EF and FS began to reduce in group I 14 days after, it continued to increase in both group II and group III. Absolute value of LVEDP at 21 days after treatment was increased in group I, group II and group III compared to group IV (5.3 mm Hg +/- 1.2 mm Hg, 6.0 +/- 1.3 mm Hg, 6.2 mm Hg +/- 1.2 mm Hg versus 1.5 mm Hg +/- 0.2 mm Hg, P < 0.05), as well as absolute value of DP/dtmin (4756 mm Hg/s +/- 270 mm Hg/s, 5028 mm Hg/s +/- 253 mm Hg/s, 5283 mm Hg/s +/- 363 mm Hg/s versus 3201 mm Hg/s +/- 211 mm Hg/s, P < 0.05). DP/dtmax at 21 days after treatment increased in group I, group II and group III compared to group IV (6026 mm Hg/s +/- 281 mm Hg/s, 6278 mm Hg/s +/- 319 mm Hg/s, 7057 mm Hg/s +/- 389 mm Hg/s versus 5293 mm Hg/s +/- 360 mm Hg/s, P < 0.05). SERCA2a expressions and enzyme activity were significantly stronger in group I and group III than in group II and group IV. CONCLUSION: It showed that all MSC transplantation, SERCA2a gene therapy and MSC-based gene therapy could enhance cardiac function. The recovered heart function continued to improve in MSC transplantation group and MSC-based gene therapy group up to 21 days, however slowed down in single gene therapy group in 21 days. Such therapeutic tendency of MSC-based gene therapy was stronger than that of MSC transplantation. Thus, MSC proved an effective platform for the targeted delivery of therapeutic gene.

[Bone marrow mesenchymal cell transplantation reduces left ventricular remodeling in heart failure following acute myocardial infarction].

OBJECTIVE: Bone marrow mesenchymal cell (MSC) transplantation has been shown to improve heart failure but the mechanism and the subsequent effects are unclear. We tested the hypothesis that MSC transplantation reduces left ventricular remodeling through the MMP/TIMP system in heart failure following acute myocardial infarction. METHODS: Female SD rats underwent coronary artery ligation to induce myocardial infarction. Four weeks later, the rats were divided into the test group (n = 7) and the control group (n = 7), respectively. The donor MSCs were harvested and expanded from male SD rats (5 x 10(6) in 50 microl PBS) and injected into the ischemic myocardium, while the control group received the same volume of PBS. Left ventricular morphology was then evaluated in both groups through staining with H&E and Masson's trichrome. Immunohistochemical staining was used to examine the expressions of MMP2 and TIMP1, as well as type I and type III collagens, in the scar zones. The protein levels of MMP2 and TIMP1 were determined by Western blotting. RESULTS: MSC differentiated into fibroblast-like cells at 21 days after transplantation in the test group. In addition, many inflammatory cells infiltrated and aggregated in the scar area, but this effect was reduced at day 7 after transplantation. The following changes were noted in the test group compared to the control group: ejection fraction and shortening fraction were higher [(63.43 +/- 3.97)% vs. (36.20 +/- 3.99)%, (31.71 +/- 1.98)% vs. (18.00 +/- 2.07)%, P < 0.05]; dp/dt(min) was reduced [(-4756.24 +/- 270.00) mm Hg/s vs. -2789.53 +/- 624.13) mm Hg/s, P < 0.05]; the left ventricular thinning ratio was significantly higher [(76.34 +/- 2.66)% vs. (64.37 +/- 2.36)%, P < 0.05]; the infarct size was smaller [(36.19 +/- 0.83)% vs. (42.12 +/- 1.88)%, P < 0.05]; type I collagen expression in the scar area was much higher; type III collagen expression was much lower; MMP2 expression was reduced and TIMP1 expression was increased. CONCLUSION: MSC transplantation led to dynamic changes in the collagen network through regulation of MMP2/TIMP1 system and consequently interrupted the progress of adverse LV remodeling in heart failure following acute myocardial infarction.