[Modified classification, screening, prevention and treatment of cardioembolic stroke].

Ischemic stroke is usually regarded as a neurological disease, but cardiogenic cerebral embolism is actually one of the most common identifiable causes of ischemic stroke. According to the origin of embolus (left heart/right heart system) and related structural abnormalities, this article expanded and refined the classification definition of cardiogenic cerebral embolism, and proposed an improved classification method of ischemic stroke (PUMCH-ISC). In addition, this article gave a practical clinical screening program for cardiovascular physicians according to different causes of stroke, and sorted out the prevention and treatment strategies and progress of common causes of cardiogenic cerebral embolism, aiming to help cardiovascular physicians and neurologists improve the screening, diagnosis and accurate prevention and treatment of cardiogenic cerebral embolism.

[The application value of cardiac magnetic resonance quantitative T1 mapping technique for risk stratification in patients with pulmonary arterial hypertension].

Objective: To explore the application value of cardiac magnetic resonance (CMR) native T1 mapping for risk stratification in patients with pulmonary arterial hypertension (PAH). Methods: A total of 59 patients with diagnosed PAH and clear-documented risk status in Peking Union Medical College Hospital and underwent CMR examination between January 2019 and December 2021 were retrospectively included, which including 12 males and 47 females, aged from 4 to 77 (31±13) years. Those patients were subdivided into two groups based on the clinically-assessed risk status: low-risk group (n=30) and intermediate-/high-risk group (n=29). Twenty-five healthy individuals were included as controls. Base, midventricular, and apical inferior right ventricular insertion point (IRVIP) native T1 values on short axis images were measured. Native T1 values in PAH patients and control group, in low-risk group and intermediate-/high-risk group were compared, respectively, and receiver operating characteristics (ROC) curves with area under the curves (AUC) were calculated to evaluate the application value of native T1 values for risk stratification in PAH patients. Results: Base, midventricular and apical IRVIP native T1 of PAH patients were all significantly increased as compared to controls [Base:(1 439.31±129.96) vs (1 282.36±37.18) ms;midventricular:(1 450.32±111.55) vs (1 287.56±53.16) ms;apical:(1 444.12±109.15) vs (1 266.36±75.31) ms](all P<0.001). The midventricular IRVIP native T1 values were significantly higher in patients in intermediate-/high-risk status as compared to those in low-risk status [ (1 493.24±126.32) vs (1 428.50±85.73) ms,P=0.026]. The AUC of mid ventricle IRVIP native T1 for distinguishing patients in intermediate-/high-risk status was 0.741. The base [(1 458.21±134.96) vs (1 421.03±104.75) ms, P=0.241] and apical [(1 465.90±125.36) vs (1 423.07±87.87) ms,P=0.136] IRVIP native T1 values in patients in intermediate-/high-risk group were also numerically higher as compared with patients in low-risk status, however, without statistical significant (both P>0.05). Conclusion: Midventricular IRVIP native T1 value might have a role for assisting in risk stratification in PAH patients, which was clinically significant for facilitating the work-up and prognosis improvement of PAH patients.

[Feasibility and safety of right ventricular endomyocardial biopsy via the right internal jugular vein approach].

Objective: To evaluate the feasibility and safety of right ventricular endomyocardial biopsy (EMB) via the right internal jugular vein approach. Methods: It was a retrospective and descriptive study. A total of 272 patients, who underwent right ventricular EMB from December 2014 to June 2020 in Fuwai Hospital and Peking Union Medical College Hospital were enrolled. The preliminary diagnosis included suspected myocarditis, myocardiopathy, unexplained heart failure etc after exclusion of coronary heart disease. Clinical characteristics including age, sex, height, weight, NYHA functional class, NT-proBNP, chest radiography, echocardiography, and hemodynamics parameters were collected at baseline. EMB was performed via right internal jugular vein approach under the biplane fluoroscopic guidance. Success rate was calculated in this study. Complications related to operation were recorded according the following definitions. Major complications included death, urgent cardiac surgery, advanced cardiac life support, pericardiocentesis in cardiac tamponade, permanent complete atrioventricular block requiring permanent pacing etc. Minor complications included pericardial effusion without pericardiocentesis, temporary (lasting less than 24 hours) or permanent right bundle-branch block, temporary Mobitz type Ⅱ atrioventricular block (AV block) with AV conduction 2∶1 requiring medical treatment with atropine, or additive temporary pacing, non-sustained ventricular tachycardia with long runs of more than 10 ventricular complexes, and an episode of atrial fibrillation lasting less than 12 hours or cardioversion of atrial fibrillation. Other complications included tricuspid anterior chorda rupture and new onset tricuspid regurgitation after EMB. Results: In this study, right ventricular EMB were performed successfully in 270 patients, the total success rate was 99.3% (270/272), and EMB were failed in 2 (0.7%) patients. Age of the enrolled patients was (42.7±16.9) years, and there were 164 (60.3%) males. Major complication including cardiac tamponade requiring pericardiocentesis occurred in 2 (0.7%) patients. Minor complications such as small amount pericardial effusion occurred in 18 (6.6%) patients, tricuspid anterior chorda rupture occurred in 1 (0.4%) patient. No patient died, or requiring permanent pacing, or requiring emergency cardiac surgery. The complication rate was 9.3% (13/140), 7.8% (7/90), and 2.4% (1/42) in operators with 1, 2, and 3 years' experience. Conclusions: EMB via the right jugular vein approach under fluoroscopic guidance is a simple, safe and feasible procedure. The complication rates decrease significantly with increasing operator experience.

[Feasibility of the determination of plasma vardenafil level in rat by performance liquid chromatography-tandem mass spectrometry].

Objective: To develope and validate a reliable and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of vardenafil concentration in plasma of rat. Methods: Plasma samples of normal Sprague-Dawley rats were collected. A Phenomenex Synergi Polar-RP 80A column (2.0 mm×50 mm, 4 µm) was used. Column temperature was set at 30 ℃. Mobile phase A was 0.1% formic acid in water; mobile phase B was 0.1% formic acid in acetonitrile. The flow rate was 0.4 ml/minutes. Quantitative determination was performed by electrospray ionization, operating in positive ion multiple reaction monitoring (MRM) mode. Cisapride was used as the internal standard. The feasibility of the method was evaluated by examining its specificity, linearity and quantitative range, precision and accuracy, matrix effects, and stability. Results: Under the selected chromatographic and mass spectrometry conditions, the monitoring ions of vardenafil and internal standard were mass-to-charge ratio（m/z) 489.3/151.2 and 466.4/234.2, the retention times of vardenafil and internal standard were 2.62 and 2.80 minutes, respectively, and the peak shape was satisfactory. The method has good linearity in the concentration range of 0.2-200 ng/ml. The intra-batch precision (%CV) and accuracy (%DEV) of vardenafil were 1.5%-9.7% and -6.8%-6.6%, respectively. The inter-batch precision and accuracy of vardenafil were 3.1% -8.4% and -3.7%-4.6%, respectively. In this sample processing method, the extraction recovery rate of vardenafil was obtained at range of 88.2%-104.6%, which met the requirements for the investigation of extraction recovery rate. In this sample processing method, the normalized matrix factor of each quality control concentration of vardenafil was 1.04, 0.85, and 1.04, and the coefficient of variation (%CV) was in the range of 1.7%-10.7%, which met the requirements for the investigation of matrix effects. Variations of short-term stability, long-term stability, and stability of 4 freeze-thaw cycles of vardenafil was within ±15%, and the coefficient of variation were within 5%. Conclusion: The high performance liquid chromatography-tandem mass spectrometry method established in this study is feasible for the measurement of concentration of vardenafil in rat plasma and this method has good specificity and high accuracy, and can be used to detect the concentration of vardenafil in rat plasma.

[Establishment of a model of hydrogen peroxide-induced injury in pulmonary artery endothelium cells and relevant mechanisms of oxidative stress].

Objective: To establish a hydrogen peroxide (H(2)O(2)) induced injury model of pulmonary artery endothelial cells (PAECs) and explore the molecular mechanisms of oxidative stress on the structure and function of PAECs in this model. Methods: Human PAECs were treated with H(2)O(2) at different concentrations (25, 50, 100, 200, 400, 800, 1 600, 3 200, 6 400 µmol/L) for 4 and 24 h, respectively. The PAECs survival curve was obtained according to the cell viability measured by CCK-8 assay. The cell apoptosis of PAECs was detected by flow cytometry. The reactive oxygen species (ROS) generation and mitochondrial activity were measured using small molecule fluorescent probes. Proteins were extracted and the phosphorylation levels of signal molecules in PAECs were detected by Western blot assays. Results: (1) The effect of H(2)O(2) at various concentrations on cell viability of PAECs: cell viability of PAECs decreased in proportion to increasing concentration of H(2)O(2) after incubation for 4 h. The half maximal inhibitory concentration (IC(50)) of PAECs exposed to H(2)O(2) for 4 and 24 h were 397.00 and 488.77 µmol/L, respectively. (2) The effect of H(2)O(2) on cell apoptosis of PAECs: After H(2)O(2) incubation for 4 h, proportions of PAECs at late-apoptosis ((22.58±3.69) %) and necrotic stage( (11.86±4.27)%) were significantly higher than those of control PAECs at late-apoptosis stage( (3.41±1.44)%, P<0.01) and at necrotic stage ((1.94±1.15) % , P<0.05). The survival rate of PAECs post H(2)O(2) was dramatically lower than that of control PAECs ((7.98±3.21)% vs. (48.89±8.08)%, P<0.01). However, there is no statistical difference between both groups regarding to the early apoptosis. (3) The effect of H(2)O(2) on mitochondrial activity and ROS production of PAECs: the mitochondrial activity and ROS generation of PAECs treated by H(2)O(2) were significantly increased compared to those in control PAECs (P<0.01). (4) The effect of H(2)O(2) on signaling molecules in PAECs: there was a significant increase in phosphorylation level of Akt in PAECs incubated with H(2)O(2) for 30 minutes compared to that in control PAECs (P<0.01), while there was no significant difference in levels of Akt between H(2)O(2) treated PAECs and control PAECs. Phosphorylation level of JNK as well as p38 were also significantly upregulated in H(2)O(2) treated PAECs (P<0.01). Conclusion: H(2)O(2) at the concentration of 400 µmol/L could induce human PAECs injuries via the regulation of Akt and MAPK signaling pathways.

[Clinical efficacy and safety of thrombolytic treatment with reteplase in patients with intermediate-risk acute pulmonary embolism].

Objective: To assess the efficacy and safety of thrombolytic treatment with reteplase in patients with intermediate-risk acute pulmonary embolism. Methods: Ten consecutive patients with intermediate-risk acute pulmonary embolism who received thrombolytic treatment with reteplase at Thrombosis and Vascular Medicine Center, Fuwai Hospital from March to November in 2016 were included.Vital signs, right ventricular diameter, systolic pulmonary artery pressure, and biochemical markers were assessed before and after thrombolytic therapy with reteplase, and bleeding complications were also observed during 3 months follow up. Results: (1) For the efficacy outcomes: at 48 hours after thrombolytic treatment with reteplase, echocardiography-derived diameter of right ventricular was significant reduced from (27.9±3.8) mm to (24.8±2.6) mm (P=0.03), systolic pulmonary artery pressure decreased from (63.9±21.6) mmHg(1 mmHg=0.133 kPa) to (34.4±19.8) mmHg (P=0.02). Heart rate and breathing rate were also decreased significantly (both P<0.05), blood pressure remained unchanged post therapy.Hypoxemia was quickly corrected with an significant elevation of PaO(2) and SaO(2) ((65.2±14.3) mmHg vs. (80.0±9.6) mmHg, P=0.006; (90.8±3.5)% vs. (95.2 ±1.6)%, P=0.002 respectively). PaCO(2) was also increased significantly (P<0.05). Serum NT-proBNP and cTnI were decreased significantly (both P<0.05). There was no recurrent pulmonary embolism or deep-vein thrombosis during the 3 months follow-up. (2) For the safety outcomes: a thrombolytic relevant hemoptysis (about 70 ml) occurred in 1 patient, and was controlled by PCC therapy.No other clinically relevant events were observed during thrombolytic treatment. Eight patients were followed more than 3 months, there was no major bleeding complication or death during the follow up period. Conclusion: Treatment of intermediate-risk acute pulmonary embolism with reteplase is effective and safe and there are no obvious side effects.

Evaluation of efficacy, safety and tolerability of Ambrisentan in Chinese adults with pulmonary arterial hypertension: a prospective open label cohort study.

BACKGROUND: Although several new drugs have been approved in recent years, pulmonary arterial hypertension (PAH) remains a rapidly progressive disease with a poor prognosis. Ambrisentan, a selective endothelin type A antagonist, has been approved for treatment of PAH. This open label study assessed the efficacy and safety of ambrisentan in Chinese subjects with PAH. METHODS: Eligible patients with PAH (World Health Organisation [WHO] functional class [FC] II orIII) were enrolled and received Ambrisentan (5 mg) once daily for a 12-week preliminary evaluation period, and a 12-week dose-adjustment period (dose titration to 10 mgallowed). Endpoints included: change from baseline in 6-Minute Walk Distance (6-MWD), N-Terminal Pro B-Type Natriuretic Peptide (NT-pro-BNP), WHO FC, Borg Dyspnoea Index (BDI), clinical worsening of PAH and incidences of adverse events (AE). RESULTS: One hundred thirty-three subjects (85 % women, mean age: 36 years) with PAH (WHOFC II or III) were enrolled and received ambrisentan (5 mg) once daily for a 12-week preliminary evaluation period, and a 12-week dose-adjustment period. Mean (SD) duration of drug exposure was 161.7 (27.13) days. Ambrisentan (average daily dose of 6.27 mg) significantly improved exercise capacity (6MWD) from baseline (mean: 377.1 m [m]) at week 12 (+53.6 m, p < 0.001) (primary endpoint). Improvement in exercise capacity was noted as early as week 4, and was sustained up to week 24 (+ 64.4 m, p < 0.001). NT-pro-BNP plasma levels decreased significantly (p < 0.001) at week 12 (-861.4 ng/L) and week 24 (-806 ng/L) from baseline (mean: 1600.7 ng/L). The WHO FC showed improvements for 44 subjects at week 12 and 51 subjects at week 24. BDI scores decreased significantly at week 12 (-0.3, p < 0.001) and week 24 (-0.2, p = 0.003) from baseline (mean: 2.5). Four patients died during the study (sudden cardiac death [n = 2], cerebral haemorrhage [n = 1], cardiac failure [n = 1]). Drug related adverse events occurred in 34.3 % of subjects; peripheral oedema (11.2 %) and flushing (8.2 %) occurred most frequently. CONCLUSION: Ambrisentan (5 and 10 mg, orally) significantly improved the exercise capacity in Chinese PAH subjects with a safety profile similar to that observed in global studies. TRIAL REGISTRATION: NCT No. (ClinicalTrials.gov): NCT01808313 ; Registration date (first time): February 28, 2013.

Common genetic risk factors of venous thromboembolism in Western and Asian populations.

Venous thromboembolism (VTE) is a multifactorial disorder involving both acquired and genetic risk factors. The common genetic factors in Western populations have been studied and reported for several decades, while studies on Asian populations are relatively scarce. Evidence suggests that the prevalence and genetic risk factors of VTE vary significantly among ethnic populations. In this review, we summarize the common genetic risk factors of VTE in both Western and Asian populations. In addition to the development of DNA sequencing technology, genome-wide association studies have many advantages and are becoming more important in identifying new genetic risk factors and susceptible loci. They can therefore help in the prediction and prevention of VTE.

[A novel open chest method of right ventricular hemodynamics measurement in pulmonary hypertensive mice].

Objective: Right heart catheterization is the gold-standard for measurement of right ventricular hemodynamics. However, it is difficult to perform in mice. We thus aimed to establish a new open chest method to record and analyze the right ventricular hemodynamic parameters in intubated mice connected to a respirator under anesthesia. Methods: Eight-week old male C57BL/6 mice were divided into the control group, and the hypoxia group using completely random method. Mice in the hypoxia group were exposed in low pressure oxygen chamber, which simulated the environment of plateau (5 500 m altitude, 10% oxygen) for 3 weeks. Mice in the control group were exposed in normal pressure and oxygen environment. The mice were intratracheally intubated and connected to a respirator, chest was opened, right ventricular hemodynamics were measured with a needle (0.7 mm×19 mm) punctured into right ventricle (5 mm in death), which was connected to the measuring equipment. Results: The open chest procedure could be finished within 5-10 minutes. The successful rate was 100%. There was no significant difference in heart rate between control group and hypoxia group under anesthetia ((306.4±11.5) bpm vs.(320.4±16.0) bpm, P>0.05). Compared with the control group, both the right ventricular systolic pressure (RVSP) and the mean right ventricular pressure(mRVP)were increased in hypoxia group ((17.1±1.0)mmHg(1 mmHg=0.133 kPa) vs. (22.6±1.0) mmHg, P<0.01; (9.6±0.8) mmHg vs.(12.4±0.3) mmHg, P<0.01). Moreover, the absolute value of the maximal rate of increase in right ventricular pressure (dp/dtmax) and the maximal rate of decrease in right ventricular pressure (dp/dtmin) were higher in the hypoxia group ((421.3±30.6)mmHg/s vs.(639.7±47.7)mmHg/s, P<0.01; (-324.3±24.0)mmHg/s vs. (-496.5±40.6) mmHg/s, P<0.01), indicating the pathological status after hypoxia treatment. Conclusions: Right ventricular hemodynamics measurement with this open chest technique is easy to handle and can accurately reflect the right ventricular pressure in mice under physiological and pathological conditions.