Left atrial strain parameters to predicting elevated left atrial pressure in patients with atrial fibrillation.

OBJECTIVES: To assess the ability of left atrial (LA) strain parameters to discriminate patients with elevated left atrial pressure (LAP) from patients with atrial fibrillation (AF). METHODS AND RESULTS: A total of 142 patients with non-valvular AF who underwent first catheter ablation (CA) between November 2022 and November 2023 were enrolled in the study. Conventional and speckle-tracking echocardiography (STE) were performed in all patients within 24 h before CA, and LAP was invasively measured during the ablation procedure. According to mean LAP, the study population was classified into two groups of normal LAP (LAP < 15 mmHg, n = 101) and elevated LAP (LAP ≥ 15 mmHg, n = 41). Compared with the normal LAP group, elevated LAP group showed significantly reduced LA reservoir strain (LASr) [9.14 (7.97-11.80) vs. 20 (13.59-26.96), p < .001], and increased LA filling index [9.60 (7.15-12.20) vs. 3.72 (2.17-5.82), p < .001], LA stiffness index [1.13 (.82-1.46) vs. .47 (.30-.70), p < .001]. LASr, LA filling index and LA stiffness index were independent predictors of elevated LAP after adjusted by the type of AF, EDT, E/e', mitral E, and peak acceleration rate of mitral E velocity. The receiver-operating characteristic curve (ROC) analysis showed LA strain parameters (area under curve [AUC] .794-.819) could provide similar or greater diagnostic accuracy for elevated LAP, as compared to conventional echocardiographic parameters. Furthermore, the novel algorithms built by LASr, LA stiffness index, LA filling index, and left atrial emptying fraction (LAEF), was used to discriminate elevated LAP in AF with good accuracy (AUC .880, accuracy of 81.69%, sensitivity of 80.49%, and specificity of 82.18%), and much better than 2016 ASE/EACVI algorithms in AF. CONCLUSION: In patients with AF, LA strain parameters could be useful to predict elevated LAP and non-inferior to conventional echocardiographic parameters. Besides, the novel algorithm built by LA strain parameters combined with conventional parameters would improve the diagnostic efficiency.

Breeding of a thermostable xylanase-producing strain of Myceliophthora thermophila by atmospheric room temperature plasma (ARTP) mutagenesis.

Introduction: Hemicellulose is an important component in lignocellulose materials, which is second only to cellulose, accounting for 15%-35% of the dry weight of plants. In the current situation of energy shortage, making full use of lignocellulose materials to produce fuel ethanol has become an important way to solve the energy problem. Xylanase plays a crucial role in the utilization of hemicellulose. It is a necessary means to reduce the cost of hemicellulose utilization by improving the activity of xylanase. Moreover, most naturally xylanases are mesophilic enzymes, which limits their industrial application. Methods:In this study, Myceliophthora thermophila was used to produce xylanases and a thermostable mutant M 2103 was obtained by atmospheric room temperature plasma (ARTP) mutagenesis. The research work started with exploring the effects of ARTP mutagenesis on the antioxidase system [superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), polyphenol oxidase (PPO), and antioxidant capacity (AOC)] of M. thermophile, and found that superoxide dismutase activity increased by 221.13%, and polyphenol oxidase activity increased by 486.04% as compared with the original strain when the implantation time was 300 s. So as to determine the conditions for subsequent mutagenesis. Results and Discussion:For the mutant M 2103, the reaction temperature for xylanase production remained stable in the range of 70°C-85°C. Its optimum temperature was 75°C, which was 15°C higher than that of the original strain. And its xylanase activity increased by 21.71% as compared with the original strain. M 2103 displayed a significantly higher relative xylanase activity than the original strain in the acidic (pH 4.0-7.0) range, and the xylanase activity was relatively stable in the pH range of 6.0-8.5. These results provide an alternative biocatalyst for the production of xylooligosaccharide, and a potential usage of ARTP in the mutagenesis of thermostable mutant.

Comparative strategies for stem cell biodistribution in a preclinical study.

Stem cell therapy represents the potential alternative effective strategy for some diseases that lack effective treatment currently. Correspondingly, it is crucial to establish high-sensitive and reliable quantification assay for tracing exogenous cell migration. In the present study, we first used both bioluminescence imaging (BLI) indirect labeling (human norepinephrine transporter-luciferase reporter system) and 89zirconium (89Zr)-hNSCs direct labeling combined with positron emission tomography/computer tomography (PET/CT) system for tracking human neural stem cells (hNSCs) migration into the brain via nasal administration in preclinical study. But the above two methods failed to give the biodistribution profile due to their low sensitivity. Considering its superior sensitivity and absolute quantitation capability, we developed and validated the droplet digital PCR (ddPCR) targeting species-specific gene in frozen and paraffin sections, slices, and whole blood with the sensitivity of 100-200 hNSCs. Accurate and high throughput quantification could be performed using ddPCR with the coefficient of variation (CVs) of lower quality control (LQC) below 30%. In combination with immunohistochemistry and ddPCR, we confirmed the migration of hNSCs into the brain via nasal administration, which supported the efficacy of hNSCs in MPTP-treated mice, an animal model of Parkinson's disease. In conclusion, the present study is the first to report the application of ddPCR in the pharmacokinetics profile description of tracking of hNSCs in preclinical studies.

Red blood cell distribution width predicts survival in patients with Eisenmenger syndrome.

BACKGROUND: Previous studies identified an independent relationship between red blood cell distribution width (RDW) and prognosis in patients with pulmonary hypertension of mixed etiologies and idiopathic pulmonary arterial hypertension. This study aimed to investigate the significance of RDW for predicting survival in patients with Eisenmenger syndrome (ES). METHODS: We retrospectively reviewed the clinical records and collected baseline data for patients newly diagnosed with ES in our hospital between January 2005 and October 2009. Follow-up data were collected periodically using a specifically designed network database until December 31, 2012. The end point was all-cause death. RESULTS: A total of 109 patients with ES were included in the study. Twenty-one patients (19.3%) died during a median follow-up period of 4.2 years (interquartile range 3.7-5.0 years). Baseline RDW was significantly correlated with mixed venous oxygen saturation (r=-0.286, p=0.003), arterial oxygen saturation (r=-0.423, p<0.001), mean pulmonary arterial pressure (r=0.271, p=0.004) and total pulmonary resistance (r=0.465, p<0.001). The 1-, 3- and 5-year survival rates for all 109 patients were 94%, 87% and 78%, respectively. Kaplan-Meier analysis showed that patients with RDW ≥13.9% had a lower survival rate than patients with RDW <13.9% (p=0.001). Multivariate Cox regression analysis showed that RDW was an independent prognostic marker in ES, with a hazard ratio of 1.162 (95% CI 1.036-1.302; p=0.010). CONCLUSIONS: Baseline RDW correlates with hemodynamics and is an independent prognostic marker in ES.

Impact of sildenafil on survival of patients with Eisenmenger syndrome.

The favorable effects of short-term use of sildenafil on patients with Eisenmenger syndrome have been reported. We further studied the impact of long-term use of sildenafil on survival of these patients. In this study, the baseline data of patients newly diagnosed as Eisenmenger syndrome in our hospital between January 2005 and December 2009 were retrospectively collected. Patients were followed-up either by telephone contacts or during visits in our out-patient clinic. A total of 121 patients (68 patients in conventional group and 53 patients in sildenafil group) were finally included and 29 patients were re-evaluated after sildenafil therapy for 3-4 months. Compared with the baseline, a 6-minute walk distance, functional classes, plasma hemoglobin level, and hemodynamics were significantly improved after sildenafil treatment. During a median follow-up period of 35.8 months, 15 patients died (11 patients in conventional group). The 1- and 3-year survival rates in sildenafil group were 97.0% and 95.2%, significantly higher than 90.6% and 82.9% in conventional group P = .025). Multivariate analysis showed that sildenafil therapy, functional class and mean pulmonary arterial pressure were independently associated with survival. Therefore, long-term sildenafil therapy improved survival in patients with Eisenmenger syndrome.

[Clinical analysis of 150 patients with idiopathic pulmonary arterial hypertension].

OBJECTIVE: To explore the demographic characteristics and clinical features of patients with idiopathic pulmonary arterial hypertension (IPAH) in China. METHODS: Between March 2007 and September 2010, IPAH diagnosis was confirmed by right heart catheterization in 150 adult patients from 31 clinical centers in China. Clinical and hemodynamic data were analyzed and patients were divided into WHO functional class I/II and WHO functional class III/IV group. RESULTS: The mean age of 150 patients were 36 ± 13 years with female patient/male patient ratio of 2:1, and mean BMI was (21.3 ± 3.5) kg/m(2). Fatigue (n = 123, 82.0%) and dyspnea (n = 112, 74.7%) are the most common symptoms. Accentuated pulmonic second sound (P(2)) was detected in 92.0% (n = 138) of patients during physical examination, which was also the most common sign. About 49.0% (n = 73) patients were WHO functional class I/II patients and 46.0% (n = 68) patients were WHO functional class III/IV patients. Six minutes walking distance (6MWD) and Borg dyspnea score was (337 ± 101) m and 2.0 (2.0, 4.0), respectively. Right ventricular hypertrophy was suggested by ECG in 93.1% (n = 140) patients. Right atrial pressure was (10 ± 6) mm Hg, mean pulmonary artery pressure was (61 ± 16) mm Hg, cardiac index was (2.3 ± 0.8) L×min(-1)×m(-2) and pulmonary vascular resistance (1484 ± 699) dyn×s(-1)×cm(-5) in this cohort. 6 MWD (305 m ± 89 m vs. 377 m ± 88 m) was significantly shorter while Borg dyspnea score [3.0 (3.0, 5.0) vs. 2.0 (2.0, 3.0)] was significantly higher in WHO functional class III/IV patients than in WHO functional class I/II patients. Similarly hemodynamic parameters were also worse in WHO functional class III/IV patients than in WHO functional class I/II patients (all P < 0.05). CONCLUSION: Idiopathic pulmonary arterial hypertension patients in this cohort affect mostly young adults, dominated by female gender and lower body mass index. Fatigue and dyspnea are the most common symptoms and accentuated pulmonic second sound (P(2)) is the most common sign. IPAH patients are often displaying severe functional and hemodynamic disturbance at first visit to hospitals. Dyspnea and hemodynamic impairment are related to 6MWD and WHO functional class.

The impact of pulmonary arterial hypertension-targeted therapy on survival in Chinese patients with idiopathic pulmonary arterial hypertension.

The survival rates of Chinese patients with idiopathic pulmonary arterial hypertension (IPAH) and familial pulmonary arterial hypertension (PAH) on conventional therapy at 1 and 3 years were 68.0% and 38.9%, respectively. Our aim was to update recent knowledge on the demographics, clinical course, hemodynamic features, disease management, and survival of adult patients with IPAH. This retrospective and observational study was conducted at the largest tertiary referral center in China. Ninety patients with IPAH who underwent initial evaluation at Fu Wai Hospital from January 2006 through November 2009 were retrospectively enrolled. The primary outcome was death. Statistical analyses used included independent sample t test, nonparametric test, Kaplan-Meier method, and Cox proportional hazards analysis. Of the 90 patients enrolled, the median age was 32 years with female predominance. The median interval from onset of symptoms to diagnosis was 14 months. Patients exhibited severe exercise limitation and hemodynamic abnormalities at diagnosis. Only 10.6% had a positive vasoreactivity test, while calcium channel blockers were given to 22.2% of patients. Fifty-nine patients (65.6%) received PAH-targeted therapies during follow-up. Our survival rates of 84.1%, 73.7%, and 70.6% at 1-, 2-, and 3-years compared favorably with predicted survival based on the National Institutes of Health equation which showed 1-, 2-, and 3-years survival rates of 67.7%, 55.9%, and 47%, respectively. For the patients receiving conventional therapy solely, the 1- and 3-years survival rates were 67.0% and 49.3%, respectively. Younger age, lower body mass index, presence of pericardial effusion, and absence of PAH-targeted therapy were independently associated with mortality. We concluded that patients with IPAH were still diagnosed too late, and while survival rates have improved in the modern treatment era, there is still room for improvement.

[Multicenter study of disease attributes in adult patients with pulmonary hypertension].

OBJECTIVE: To understand the demographic, hemodynamic and clinical features of adult patients with pulmonary hypertension (PH) in China. METHODS: Between May 2007 and October 2010, a total of 551 adult PH patients were recruited from 31 clinical centers all over China. All fulfilled the traditional hemodynamic criteria diagnosed through right heart catheterization (RHC). The relevant data of demographic, clinical and hemodynamic features of all patients, analyzed the similarities and differences of demographic characteristics between different subtypes. They were divided into 2 groups: WHO functional class I/II and III/IV. And their hemodynamic and clinical features were compared. RESULTS: There were 165 males and 386 females with a mean age of (35 ± 12) years. The mean body mass index (BMI) was (21 ± 4) kg/m(2). There were pulmonary arterial hypertension (PAH, n = 487) and chronic thromboembolic pulmonary hypertension (CTEPH, n = 64). Fatigue (421, 76.4%) and dyspnea (398, 72.2%) were the most common symptoms; Physical examination revealed such a common sign as an accentuated pulmonic second sound (P(2)) in 510 patients (92.6%). Over half (325, 59.0%) of them were of WHO functional class II and 213 (38.6%) patients functional class III. The 6-minute walking distance (6MWD) and Borg dyspnea score were (352 ± 91) m and 3.0 (2.0 - 4.0) respectively. ECG of 497 (90.2%) patients showed right ventricular hypertrophy. Mean right atrial pressure was (9 ± 6) mm Hg (1 mm Hg = 0.133 kPa), pulmonary arterial pressure (67 ± 20) mm Hg, cardiac index (2.7 ± 1.2) Lmin(-1)m(-2) and pulmonary vascular resistance (1496 ± 783) dyn.sec.cm(-5). CONCLUSIONS: Young females with a low BMI are predominantly affected by PH. Severe functional and hemodynamic compromises often appear on presentation. And hemodynamic impairment is correlated with 6MWD and WHO functional class.

[Screening study of pulmonary arterial hypertension in patients with congenital heart diseases].

OBJECTIVE: To determine the prevalence and influencing factors of pulmonary arterial hypertension (PAH) in patients with congenital heart disease (CHD). METHODS: Between May 2007 and December 2008, a total of 692 CHD patients admitted into Fuwai Hospital were prospectively enrolled. Doppler echocardiography was employed to measure the level of pulmonary artery systolic pressure (PASP). PAH occurred when there was an increase in PASP > 40 mm Hg (1 mm Hg = 0.133 kPa) at rest. Eisenmenger syndrome was defined when there was a reversed (pulmonary-to-systemic) or bidirectional shunt. The clinical characteristics between the patients with/without PAH and Eisenmenger syndrome were compared and their risk factors analyzed with a multivariate Logistic model. RESULTS: The underlying conditions included atrial septal defect (n = 187, 27.0%), ventricular septal defect (n = 456, 65.9%) and patent ductus arteriosus (n = 49, 7.1%). The numbers of patients with PAH-CHD and Eisenmenger syndrome were 329 (47.5%) and 105 (15.2%) respectively. Among the PAH-CHD patients, 31.9% of them had Eisenmenger syndrome. The patients with large shunts were at an elevated risk of PAH. Logistic regression analysis showed that advanced age was an independent risk factor of PAH (OR = 1.04, P < 0.001). Compared with atrial septal defect, ventricular septal defect and patent ductus arteriosus increased the risks of PAH (OR = 2.78, P < 0.001 and OR = 2.50, P < 0.001 respectively). CONCLUSIONS: PAH is a common complication in CHD patients. And ventricular septal defect is the most common pathogenic type of PAH. Advanced age, ventricular septal defect and patent ductus arteriosus are the risk factors of PAH.

Inhaled low-dose iloprost for pulmonary hypertension: a prospective, multicenter, open-label study.

BACKGROUND: Inhaled iloprost (average >30 µg/d) has been considered an effective treatment for severe pulmonary hypertension (PH). Further evidence also showed that low-dose iloprost given intravenously was equally effective as high-dose iloprost in the therapy of systemic sclerosis. HYPOTHESIS: Patients with pulmonary hypertension will benefit from inhalation of low-dose iloprost. METHODS: Sixty-two patients with PH were enrolled and initiated with neubulizedlow-dose iloprost (2.5 µg per inhalation, 6× daily) for 24 weeks in 13 medical centers in China. Efficacy endpoints included changes in 6-minute walk distance (6MWD), World Health Organization functional class (WHO-FC), and hemodynamic parameters. RESULTS: Fourteen patients (22.6%) prematurely discontinued the study: 8 due to clinical worsening (6 in WHO-FCIII-IV at baseline), 4 because of protocol change, and 2 patients lost during follow-up. In the remaining 48 patients, 6MWD was increased from 356 ± 98 meters to 414 ± 99 meters (P < 0.001) and WHO-FC improved significantly (P = 0.006) after 24-week inhalation therapy. Cardiac output, cardiac index, and mixed venous oxygen saturation improved significantly compared with baseline (n = 34, P < 0.05). Most of the hemodynamic parameters improved significantly in patients in WHO-FC II (P < 0.05) but not in patients in WHO-FCIII-IV. CONCLUSIONS: Low-dose iloprost inhalation significantly improved exercise capacity and functional status in patients with PH. It was well tolerated. The improvement of hemodynamics was confirmed in patients with WHO-FCI-II but not in patients with WHO-FCIII-IV, suggesting the importance of early treatment in patients with advanced disease stages.

Impact of sildenafil on survival of patients with idiopathic pulmonary arterial hypertension.

It has been reported that short-term sildenafil therapy is safe and effective for patients with pulmonary arterial hypertension. However, data regarding the impact of sildenafil on the survival of patients with idiopathic pulmonary arterial hypertension remain limited. The study was conducted on 77 patients with newly diagnosed idiopathic pulmonary arterial hypertension at Fu Wai Hospital between September 2005 and September 2009. Patients were divided into 2 groups: the sildenafil group and the conventional group. Nine patients treated with sildenafil were re-evaluated by right heart catheterization after 3 months. Our data demonstrated that the 6-minute walk distance, World Health Organization functional class, mixed venous oxygen saturation, and hemodynamics significantly improved after 3 months of sildenafil therapy (P < .05). The baseline characteristics of the sildenafil group were similar to those of the conventional group. The 1-, 2-, and 3-year survival rates in the sildenafil group were 88%, 72%, and 68% compared with 61%, 36%, and 27% in the conventional group (P < .001). The absence of sildenafil therapy, lower body mass index, and lower mixed venous oxygen saturation were found to be independent predictors of mortality. In conclusion, sildenafil therapy was found to be associated with improved survival in patients with idiopathic pulmonary arterial hypertension.

[Accuracy of transthoracic Doppler echocardiography in the estimation of pulmonary artery systolic pressures].

OBJECTIVE: To investigate the qualitative accuracy of pulmonary artery systolic pressure (PASP) as estimated by transthoracic Doppler echocardiography (TDE). METHODS: A retrospective study was conducted on 102 adult patients with idiopathic pulmonary arterial hypertension undergoing Doppler echocardiography within 72 hours prior to right heart catheterization. During this period, all patients were stable without any specific drug therapy. Compared with right heart catheterization, the accuracy of PASP as measured by TDE was evaluated. RESULTS: Among them, there were 38 males and 64 females with an average age of (31 ± 11) years old (range: 18 - 59 years old). There was a moderate correlation between the measurements of PASP by TDE and right heart catheterization (r = 0.64, P < 0.01). Through the analysis of Bland-Altman, the bias for the TDE estimates of PASP was 6.7 mm Hg with a 95% limit of agreement ranging from -47.6 to 34.3 mm Hg. There were 60 (58.8%) cases with absolute differences over 10 mm Hg between two methods. Overestimation and underestimation of PASP by TDE occurred in 15.7% (16/102) and 43.1% (44/102) respectively. The magnitude of pressure underestimation and overestimation was insignificant [(25 ± 12) vs (26 ± 16) mm Hg, P = 0.765]. The probability of underestimate was higher than that of overestimate. As to the corresponding diagnostic categories of severity that each subject would fall into for each technique, the diagnostic categories of 16 overestimated patients were in accordance. Among 44 underestimated patients, 9 (20.5%) had their pressure underestimated within one diagnostic category (minor error) while 2 (4.5%) were within two diagnostic categories (major error). CONCLUSION: Due to a frequent rate of inaccurate estimation of PASP, TDE can not replace right heart catheterization. TDE tends to underestimate PASP and results in a diagnostic misclassification of degree.

Prognostic value of echocardiographic right/left ventricular end-diastolic diameter ratio in idiopathic pulmonary arterial hypertension.

BACKGROUND: An echocardiographic right/left ventricular end-diastolic diameter ratio (RV/LV ratio) ≥ 0.9 is an independent predictor of poor prognosis in patients with acute pulmonary embolism. Right ventricular dilation is a common characteristic of both acute pulmonary embolism and idiopathic pulmonary arterial hypertension (IPAH). However, the prognostic value of the RV/LV ratio in patients with IPAH is unknown. METHODS: Ninety-five consecutive patients with newly diagnosed IPAH were included, 17 were re-evaluated by echocardiography after 3 - 12 months of targeted therapy. Follow-up data were obtained by telephone interviews and review of the patients' records. RESULTS: Higher RV/LV ratios were associated with greater functional impairment. The RV/LV ratio was positively correlated with pulmonary vascular resistance (r = 0.549, P < 0.001) and plasma N-terminal pro-brain natriuretic peptide level (r = 0.575, P < 0.001), but negatively correlated with cardiac output (r = -0.517, P < 0.001) and mixed venous oxygen saturation (r = -0.599, P < 0.001). Twenty-seven patients died during follow-up period. Sensitivity and specificity of an RV/LV ratio ≥ 0.84 for predicting death were 85.2% and 51.5%, respectively. The RV/LV ratio and body mass index were independent predictors of death by multivariate Cox analysis (P < 0.01). A baseline RV/LV ratio ≥ 0.84 or a further increase in the RV/LV ratio during targeted therapy indicated a poor prognosis (P < 0.01). CONCLUSION: The RV/LV ratio helps to assess the severity of IPAH and may serve as an independent predictor of prognosis in patients with IPAH.

Overexpression of inducible heat shock protein 70 and its mutants in astrocytes is associated with maintenance of mitochondrial physiology during glucose deprivation stress.

Wild-type inducible Hsp70 (WT) and 2 folding deficient mutants protect the brain against focal cerebral ischemia in vivo and brain cells from oxygen-glucose deprivation (OGD) in vitro, but the protective mechanisms remain unclear. Mitochondria are central to both normal physiological function and the regulation of cell death. We tested the effect of overexpressing Hsp70 and 2 mutants, Hsp70-K71 E, an adenosine triphosphatase (ATPase)-deficient point mutant, and Hsp70-381-640, a deletion mutant lacking the ATPase domain on mitochondrial physiology under glucose deprivation (GD) stress in primary cultured astrocytes. Mitochondrial membrane potential was assessed using a potentiometric fluorescent dye tetramethylrhodamine ethyl ester (TMRE). By 5 hours of GD, the mitochondria in the LXSN control transfected astrocytes had markedly reduced membrane potential. However, in the Hsp70-WT, -K71E, and -381-640 groups, there was no apparent change in TMRE signal during 5 hours of GD. Oxygen consumption was measured to assess oxidative respiration. Overexpression of Hsp70-K71 E and -381-640 prevented the decrease in state III respiration observed at 5 hours, and all 3 prevented the increase in state IV respiration found in LXSN controls after 5 hours of GD. Reactive oxygen species (ROS) production was assessed with hydroethidine. Hsp70 and its mutants all significantly reduced the increases in ROS accumulation during 5 hours of GD. The results demonstrate that the protective effect of the carboxyl-terminal half of Hsp70 and of the full-length molecule is associated with better maintained mitochondrial membrane potential, better maintained state IV respiration, and reduced ROS generation during GD.