The role of immune and inflammatory-related indicators in cognitive dysfunction and disease severity in patients with parkinson's disease.

We aimed to explore the role of immune and inflammatory indicators in cognitive dysfunction and disease severity in patients with Parkinson's disease (PD). A total of 123 patients with Parkinson's disease were enrolled in the PD group and 49 healthy volunteers in the control group. The patients with PD were further divided into 2 subgroups by evaluating cognitive function using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE): the normal cognitive function (PD-NCI) group and the mild cognitive impairment (PD-MCI) group. Moreover, the PD patients were also divided into 2 subgroups using the defined scale of the Hoehn and Yahr (H-Y) stage: the early-stage group and the middle- and late-stage group. Immune and inflammatory indicators, including serum Aß1-42, Tau, CD4+, CD8+, CD3+, B lymphocytes cell, NK cell, Th17 cell, Treg cell, IL-6, IL-17, and TNF-α levels, were evaluated and analyzed to explore the potential correlation with the cognitive dysfunction and disease severity of PD. Among the 123 PD patients, 60 (48.8%) were diagnosed with mild cognitive impairment. Aß1-42, CD4+, CD8+, CD3+, and Treg levels observed in the PD-NCI group were lower than the control group (P < 0.001), while higher than the PD-MCI group (P < 0.001). The levels of Tau, Th17, IL-6, IL-17, and TNF-α observed in the PD-NCI group were higher than the control group (P < 0.001), while lower than in the PD-MCI group (P < 0.01). Using the same method, the results of the early-stage group and the middle- and the late-stage group were the same as above. Logistic regression analysis and ROC curve estimation were performed and indicated that the variation of Tau, CD8+, Treg, TNF-α levels was associated with cognitive decline in PD patients, and may serve as markers of PD onset. Furthermore, the variation of Aß1-42, IL-6, and TNF-α levels was found to correlate with the disease severity of PD. The immune and inflammatory-related indicators may represent an important factor in the pathogenesis of PD, cognitive dysfunction, and disease severity. The variation of Tau protein, CD8+, Treg, and TNF-α levels are associated with the cognitive dysfunction of PD, which may be considered as onset markers. Moreover, the variation of Aß1-42, IL-6, and TNF-α levels can predict the progression of PD.

Study on Welding Deformation and Optimization of Fixture Scheme for Thin-Walled Flame Cylinder.

In this paper, the best fixture scheme for the TIG welding torch of nickel-base solid solution superalloy GH3536 in the welding process is explored. First of all, to meet the extremely high-dimensional accuracy requirements of the flame cylinder, a multifield coupling analysis model based on the flame cylinder is established on SYSWELD software. By studying the stress and deformation of welded parts under different line constraint positions and applied pressure, the trend of welding deformation is obtained, and the relevant mathematical model is established based on this. Finally, the particle swarm optimization (PSO) algorithm is used to calculate the best fixture scheme to make the welding stress and deformation better. The simulation results show that the welding deformation is negatively related to the line constraint distance and positively related to the applied pressure. According to the optimized clamping scheme of PS0, through simulation calculation, the average axial deformation is reduced by 82.5%, the maximum radial shrinkage deformation is reduced by 60.6%, and the maximum residual stress is reduced by 60.3%. Finally, it is verified by the flame barrel experiment that it meets the acceptance requirements and successfully solves the problem of serious axial shrinkage during the TIG welding of the outer ring of the flame barrel.

The study of serum C-reactive protein, Serum cystatin C, and carbohydrate antigen 125 in patients with acute ischemic stroke.

Stroke is the most common, deadly, and complicating neurological disease. Many studies have shown that the levels of some acute inflammatory reactants in people with ischemic stroke are higher than average. Therefore, in this study, three acute inflammatory reactants, i.e., C-reactive protein, Serum cystatin C, and carbohydrate antigen 125, were evaluated in patients with acute ischemic stroke to consider the association between these serums with intra and extra-cerebral vessels stenosis. In this cross-sectional study, 90 patients with non-embolic ischemic stroke were evaluated. The diagnosis was by physical examination, rejection of emboli, and brain imaging. Blood samples were taken in the first 24 hours of a stroke. ELISA test was used to measure CRP, Serum cystatin C, and CA125. Doppler ultrasound of cerebral arteries was also performed in the first five days. Independent chi-square and t-tests were used to analyze the data. The result of CRP level in patients with stenosis was 7.58±1.33µg/ml and in patients without stenosis was 4.10±1.75µg/ml (p = 0.004). Also, there was a significant relationship between serum CRP level and stenosis (p = 0.003). In patients with abnormal CRP, the internal carotid artery, middle cerebral artery, and anterior cerebral artery were the most involved. In patients with normal CRP, the most involved arteries were the anterior cerebral artery, internal carotid artery, and middle cerebral artery, respectively. There was a significant relationship between serum CRP level and the location of internal carotid artery stenosis (p = 0.015) and middle cerebral artery (p = 0.006). The amount of cystatin C between the normal CRP and abnormal CRP groups was statistically significant so that its concentration in the normal group was less than in the abnormal group (p = 0.04). The results of measuring the serum concentration of carbohydrate antigen 125 showed that the serum level in the normal group was statistically lower than in the abnormal group (P = 0.02). The results showed that stenosis of the internal carotid artery and middle cerebral artery is more common in patients with ischemic stroke with high serum CRP levels. This finding suggests that abnormal CRP may be more associated with narrowing some cerebral arteries.

Prognostic implication of noninvasive right ventricle-to-pulmonary artery coupling in chronic thromboembolic pulmonary hypertension.

Aims: Impairment of right ventricle-to-pulmonary artery coupling (RV-PA coupling) is a major determinant of poor prognosis in patients with pulmonary hypertension. This study sought to evaluate the ability of an echo-derived metric of RV-PA coupling, the ratio between tricuspid annular plane systolic excursion (TAPSE), and pulmonary artery systolic pressure (PASP) and to predict adverse clinical outcomes in chronic thromboembolic pulmonary hypertension (CTEPH). Methods and results: A total of 205 consecutive patients with confirmed CTEPH were retrospectively recruited from Fuwai Hospital between February 2016 and November 2020. Baseline echocardiography, right heart catheterization, and cardiopulmonary exercise testing were analyzed. Patients with lower TAPSE/PASP had a significantly compromised echocardiographic and hemodynamic status and exercise capacity at baseline. The TAPSE/PASP ratio correlated significantly with hemodynamic parameters, including pulmonary vascular resistance (r = -0.48, p < 0.001) and pulmonary arterial compliance (r = 0.45, p < 0.001). During a median period of 1-year follow-up, 63 (30.7%) patients experienced clinical worsening. The relationship between TAPSE/PASP and clinical worsening was assessed using different multivariate Cox regression models. After adjustment for a series of previously screened independent predictors, TAPSE/PASP remained significantly associated with outcomes, and the hazard ratio (per standard deviation increase) of the final model was 0.402. Conclusion: In patients with CTEPH, baseline RV-PA coupling measured as the TAPSE/PASP ratio is associated with disease severity and adverse outcomes. A low TAPSE/PASP identifies patients with a high risk of clinical deterioration, and this novel metric could be applicable for risk stratification in CTEPH.

Heart-Rate Recovery at 1 Min After Exercise Predicts Response to Balloon Pulmonary Angioplasty in Patients With Inoperable Chronic Thromboembolic Pulmonary Hypertension.

BACKGROUND: Dysfunction of autonomic nervous system plays an important role in the development of pulmonary hypertension. The present study aimed to investigate the interaction between balloon pulmonary angioplasty (BPA) and cardiac autonomic function by using heart-rate recovery at 1 min (HRR1) after exercise as a surrogate marker. METHODS AND RESULTS: We retrospectively enrolled 89 consecutive patients with inoperable chronic thromboembolic pulmonary hypertension who underwent BPA from May, 2018 to Jan, 2021. According to hemodynamics at follow-up, patients were categorized as BPA responders if they met one or both of the following criteria: (1) mean pulmonary arterial pressure ≤ 30 mmHg and (2) a reduction of pulmonary vascular resistance ≥ 30%. Compared with baseline, HRR1 tended to increase within 7 days after the first BPA session, and this improvement persisted at follow-up. HRR1 at baseline and at follow-up were associated with well-validated markers of CTEPH severity, including N-terminal pro-brain natriuretic peptide, mean pulmonary arterial pressure and pulmonary vascular resistance. Furthermore, the change of HRR1 from baseline to follow-up was also associated with the change of those variables. After adjustment for confounders, baseline HRR1 was still a strong independent predictor of BPA outcome. Receiver operator characteristic curve analysis showed that the cutoff value for HRR1 in predicting BPA outcome was 19 beats. CONCLUSIONS: BPA could significantly improve HRR1, suggesting the alleviation of sympathovagal imbalance. Easily available and non-invasive HRR1 seems to be a useful tool in predicting outcome of BPA and dynamically monitoring the efficacy of BPA.

The spectrum and prevalence of arrhythmia in different clinical pulmonary hypertension groups in Chinese population.

BACKGROUND: Arrhythmia is not uncommon among pulmonary hypertension (PH) population, and may be associated with disease severity. HYPOTHESIS: To investigate different spectrums and prevalence of arrhythmias in different clinical PH groups in Chinese population. METHODS: Patients diagnosed with PH between April 15, 2019, and August 2, 2021, were enrolled prospectively. The prevalence of different types of arrhythmias in PH patients were calculated. Logistic regression analyses were conducted to determine independent predictors for arrhythmia. RESULTS: One thousand patients were enrolled. The prevalence of any arrhythmia, sinus node dysfunction, sinus tachycardia, atrial fibrillation, atrial flutter, other types of atrial tachycardia, atrioventricular block, and ventricular tachycardia is 44.4%, 12.2%, 15.2%, 8.1%, 4.1%, 10.2%, 7.1%, and 2.5%. Logistic regression analyses revealed that older age and larger right ventricle (odds ratio: 1.111 and 1.095, p < .05) were independently related with higher probability of supraventricular arrhythmia; Complicating with coronary artery disease, larger right ventricle, and increased left ventricular end-diastolic diameter (odds ratio: 19.540, 1.106, and 1.085, p < .05) were independently correlated with sinus node dysfunction/atrioventricular block in patients with pulmonary arterial hypertension. CONCLUSIONS: Nearly half of PH patients experienced at least one type of arrhythmia. The most common seen arrhythmias were supraventricular arrhythmia, sinus tachycardia, and sinus node dysfunction. Older age and larger right ventricle were independently related with higher probability of supraventricular arrhythmia; Complicating with coronary artery disease, larger right ventricle and increased left ventricular end-diastolic diameter were independently correlated with higher probability of sinus node dysfunction/atrioventricular block in patients with pulmonary arterial hypertension.

Diffusing Capacity for Carbon Monoxide Predicts Response to Balloon Pulmonary Angioplasty in Patients With Inoperable Chronic Thromboembolic Pulmonary Hypertension.

Background: The hemodynamic results of balloon pulmonary angioplasty vary among patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Previous studies revealed that microvasculopathy accounted for residual pulmonary hypertension after pulmonary endarterectomy, which could be reflected by the diffusing capacity for carbon monoxide (DLCO). We aimed to identify whether the DLCO could predict the BPA response. Materials and Methods: We retrospectively analyzed 75 consecutive patients with inoperable CTEPH who underwent BPA from May 2018 to January 2021 at Fuwai Hospital. According to the hemodynamics at follow-up after the last BPA, patients were classified as "BPA responders" (defined as a mean pulmonary arterial pressure ≤ 30 mmHg and/or a reduction of pulmonary vascular resistance ≥ 30%) or "BPA nonresponders." Results: At the baseline, BPA responders had significantly higher DLCO values than nonresponders, although the other variables were comparable. In BPA responders, the DLCO decreased after the first BPA session and then returned to a level similar to the baseline at follow-up. Conversely, the DLCO increased constantly from the baseline to follow-up in nonresponders. Multivariate logistic analysis showed that a baseline DLCO of <70% and a percent change in DLCO between the baseline and the period within 7 days after the first BPA session (ΔDLCO) of > 6% were both independent predictors of an unfavorable response to BPA. Receiver operator characteristic analysis showed that the combination of a baseline DLCO < 70% and ΔDLCO > 6% demonstrated a better area under the curve than either of these two variables used alone. Conclusions: A baseline DLCO < 70% and ΔDLCO > 6% could independently predict unfavorable responses to BPA. Measuring the DLCO dynamically facilitates the identification of patients who might have unsatisfactory hemodynamic results after BPA.

Impact of the revised hemodynamic definition on the diagnosis of precapillary pulmonary hypertension: a retrospective single-center study in China.

BACKGROUND: In the 6th World Symposium on Pulmonary Hypertension (PH), the hemodynamic definition of PH was reduced from a mean pulmonary artery pressure (mPAP) ≥25 to >20 mmHg. This study aimed to evaluate the impact of the revised hemodynamic definition on the diagnosis of precapillary PH. METHODS: We retrospectively enrolled patients who underwent right heart catheterization from January 2012 to December 2018. All included patients were reassessed according to the revised hemodynamic definition. RESULTS: A total of 1,251 patients were included for analysis, of whom 1,044 patients had precapillary PH and 182 patients had mPAP <25 mmHg. After applying the revised definition, 33 (18.1%) of 182 patients with mPAP <25 mmHg were reclassified as having PH. However, only 7 of these 33 patients had a pulmonary vascular resistance ≥3 wood units and could be considered to have precapillary PH, accounting for 0.7% of the existing precapillary PH population. More importantly, 12 patients with mPAP ≥25 mmHg were delisted from precapillary PH for pulmonary vascular resistance <3 wood units (5 patients from Group III, 4 patients from Group IV, 3 patients from Group V). Overall, there was a net 0.5% decrease [(12-7)/1044×100%] in the population with precapillary PH. CONCLUSIONS: The revised hemodynamic definition had a minor impact on the diagnosis of precapillary PH. It should be noted that the revised definition would influence not only patients with mPAP =21-24 mmHg, but also patients with mPAP ≥25 mmHg.

Carbohydrate Antigen 125 Is a Biomarker of the Severity and Prognosis of Pulmonary Hypertension.

Background: Emerging evidence has showed that serum carbohydrate antigen 125 (CA 125) levels are associated with the severity and prognosis of heart failure. However, its role in pulmonary hypertension remains unclear. This study aimed to investigate the clinical, echocardiographic, hemodynamic, and prognostic associations of CA 125 in pulmonary hypertension. Methods and Results: We conducted a retrospective cohort study of all idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension patients receiving CA 125 measurement in Fuwai Hospital (January 1, 2014-December 31, 2018). The primary end-point was cumulative 1-year clinical worsening-free survival rate. Linear regression was performed to assess the association between CA 125 and clinical, echocardiographic, and hemodynamic parameters. Cox proportional hazards models were used to assess the association between CA 125 and clinical worsening events. Receiver operating characteristic (ROC) curve analysis was performed to determine the predictive performance of CA 125. A total of 231 patients were included. After adjustment, CA 125 still positively correlated with World Health Organization functional class, NT-proBNP, right ventricular end-diastolic diameter, pericardial effusion, mean right atrial pressure and pulmonary arterial wedge pressure; negatively correlated with 6-min walk distance, left ventricular end-diastolic diameter, mixed venous oxygen saturation, and cardiac index. After adjustment, CA 125 > 35 U/ml was associated with over 2 folds increased risk of 1-year clinical worsening. Further, ROC analysis showed that CA 125 provided additional predictive value in addition to the established pulmonary hypertension biomarker NT-proBNP. Conclusion: CA 125 was associated with functional status, echocardiography, hemodynamics and prognosis of pulmonary hypertension.

The value of cardiopulmonary exercise testing in the diagnosis of pulmonary hypertension.

BACKGROUND: Cardiopulmonary exercise testing (CPET) continuously analyzes the gas exchange of patients during rest, exercise, recovery, and simultaneously records the response of the cardiopulmonary system. This study aimed to observe the characteristics of CPET in patients with pulmonary hypertension (PH) and to explore the cutoff value of CPET variables in detecting PH. The diagnostic value of CPET was also investigated in a subgroup of patients who had an incorrect or missed diagnosis of PH by echocardiography. METHODS: Treatment-naïve patients with suspected PH who were admitted to Fuwai Hospital from January 2017 to August 2018 were consecutively enrolled. The gold standard criterion for PH was defined as mean pulmonary artery pressure (mPAP) ≥25 mmHg at rest, measured by right heart catheterization. General clinical materials, echocardiography, hemodynamics, and CPET data of the patients were collected and compared between groups. Logistic regression analyses were performed to explore the CPET variables that were independently associated with PH. To further validate the value of CPET for diagnosing PH, the CPET cutoff values obtained from receiver operating characteristic (ROC) curve analysis were used in patients who had an incorrect or missed diagnosis by echocardiography. RESULTS: Five hundred and fifty-nine patients were included in the study. Among them, patients with PH had significantly poorer CPET variables. Multivariate logistic regression analysis showed that peak work rate (WR), peak oxygen uptake (VO2), and end-tidal carbon dioxide partial pressure (PetCO2) at the anaerobic threshold (AT) were independently associated with PH after adjustment for age, sex, and body mass index. The above three CPET variables were all negatively correlated with mPAP. The combined CPET variable including peak WR, peak VO2 and PetCO2 at AT had the largest area under the ROC curve for the diagnosis of PH (0.890, 95% CI: 0.852-0.927, P<0.001). The cutoff value was 0.86, and the sensitivity and specificity were 81.8% and 86.5%, respectively. Using this cutoff value, 83.7% of patients who were misdiagnosed and 67.9% of patients who had a missed diagnosis by echocardiography were identified. CONCLUSIONS: PH patients have decreased cardiopulmonary reserve, lower exercise tolerance, and increased ineffective ventilation. The combination of peak WR, peakVO2, and PetCO2 at AT had increased sensitivity and specificity for the diagnosis of PH, and increased the specificity for identifying patients who had been misdiagnosed as PH by echocardiography.

Exercise pathophysiology differs between connective tissue diseases-associated pulmonary arterial hypertension and idiopathic pulmonary arterial hypertension.

OBJECTIVES: Previous studies demonstrated that connective tissue diseases-associated pulmonary arterial hypertension (CTD-PAH) had a worse prognosis than idiopathic pulmonary arterial hypertension (IPAH), although the former one had better haemodynamic profiles and right heart function. To find potential explanations for this contradictory phenomenon, we compared the exercise pathophysiology of CTD-PAH with that of IPAH using cardiopulmonary exercise testing (CPET). METHODS: Ninety-three CTD-PAH patients were retrospectively enrolled and matched 1:1 with 93 IPAH patients according to age, gender, body mass index, and body surface area. Multiple linear regression analysis was performed to adjust confounding factors. RESULTS: CTD-PAH had higher rest heart rate (HR@Rest) and lower rest oxygen uptake/HR (VO2/HR@Rest) than IPAH. During exercise, the peak power (Power@Peak), VO2@Peak, peak metabolic equivalents (METS@Peak), peak minute ventilation (VE@Peak), peak tidal volume (VT@Peak), HR@Peak, peak systolic blood pressure (SBP@Peak) and peak diastolic blood pressure (DBP@Peak) of CTD-PAH were lower than those of IPAH. After adjustment, CTD-PAH still had lower values of Power@Peak, VO2@Peak, METS@Peak, VT@Peak, VO2/HR@Rest, DBP@Peak and had higher HR@Rest than IPAH. CONCLUSIONS: CTD-PAH had more impaired ventilation, cardiac function and muscular strength (reflected by CPET-derived parameters) than IPAH, in despite of better haemodynamic profiles and comparable heart structure (assessed by echocardiography) and functional status (indicated by World Health Organisation functional class, N-terminal pro-brain natriuretic peptide and six-minute walk distance).

Improved hemodynamics and cardiopulmonary function in patients with inoperable chronic thromboembolic pulmonary hypertension after balloon pulmonary angioplasty.

BACKGROUND: Balloon pulmonary angioplasty (BPA) has been demonstrated to improve cardiac function and exercise capacity in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), but its instant impact on cardiopulmonary function has seldom been evaluated. This study aims to determine the safety and efficacy of BPA and its immediate and lasting effects on cardiopulmonary function among CTEPH patients. METHODS: From May 2018 to January 2019, patients with inoperable CTEPH who underwent BPA sessions were consecutively enrolled. Hemodynamics were measured by right heart catheterization, selective pulmonary angiography and BPA were successively conducted. Hemodynamic variables, WHO functional class (WHO-FC), 6-min walk distance (6MWD) and serum NT-proBNP were evaluated before and after BPA sessions during hospitalization. Pulmonary function testing (PFT) and cardiopulmonary exercise testing (CPET) were performed within 1-3 days pre and post BPA to evaluate the effect of BPA on cardiopulmonary function. RESULTS: Twenty-five patients with inoperable CTEPH who underwent a total of forty BPA sessions were consecutively enrolled. A total of 183 segmental or subsegmental vessels (4.6 ± 1.9 vessels per session) in 137 segments (3.4 ± 1.6 segments per session) were dilated. No procedure-related complications occurred. Instant hemodynamics, WHO-FC, 6MWD and NT-proBNP were all significantly improved after a single BPA session. Significant improvement in cardiopulmonary function was also evident as assessed by PFT indexes (forced vital capacity, forced expiratory volume in the first second, maximal voluntary ventilation) and CPET parameters (peak work rate, peak VO2, oxygen uptake efficiency slope). Further analysis among ten CTEPH patients receiving multiple BPA sessions (2-4 sessions) indicated BPA resulted in lasting improvements in hemodynamics and cardiopulmonary function. CONCLUSIONS: BPA, a safe and effective approach, can bring instant improvements after a single session and lasting benefits after multiple sessions to hemodynamics and cardiopulmonary function for patients with inoperable CTEPH.

Peak circulatory power is a strong prognostic factor in patients with idiopathic pulmonary arterial hypertension.

BACKGROUND: Studies have shown that peak circulatory power (peak CircP; peak oxygen uptake × peak systolic blood pressure) is a variable predictor of prognosis in patients with left heart failure. It remains unknown whether peak CircP also predicts outcome in patients with idiopathic pulmonary arterial hypertension (IPAH). METHODS: Patients with newly diagnosed IPAH who underwent symptom-limited cardiopulmonary exercise testing (CPET) from 1 January 2011 to 1 January 2014 in Fuwai Hospital were prospectively enrolled and followed for up to 66 months for cardiac events (mortality and lung transplantation). RESULTS: One hundred forty patients with IPAH (104 female, mean age: 33 ±â€¯11 years) were studied. During follow-up (mean: 42 ±â€¯14 months), 24 patients died and 1 patient underwent lung transplantation. In the univariate analysis, peak oxygen uptake(VO2), oxygen uptake at anaerobic threshold, ventilation (VE)/carbon dioxide output (VCO2) slope, end-tidal partial pressure of carbon dioxide at anaerobic threshold, peak systolic blood pressure (SBP), the change of SBP, the change of heart rate, peak work rate, peak CircP, pulmonary vascular resistance, cardiac index and World Health Organization functional class were predictive of cardiac events (all P < .05).In the multivariate analysis, Peak CircP in the fourth model had the highest significance compared with peak VO2 and VE/VCO2 slope in the second and third model (chi-square = 5.26, P < .02, HR: 0.99, 95% CI: 0.99 to 1.00). CONCLUSIONS: Peak CircP, better than peak VO2 and VE/VCO2slope, was a strong predictor of cardiac events among exercise parameters in patients with IPAH.

Oxygen Uptake Efficiency Slope Predicts Poor Outcome in Patients With Idiopathic Pulmonary Arterial Hypertension.

BACKGROUND: Few published studies have evaluated the power of the oxygen uptake efficiency slope (OUES) to predict outcomes in patients with idiopathic pulmonary arterial hypertension (IPAH), who typically die of right-sided heart failure. Our study sought to evaluate the power of OUES to predict clinical worsening and mortality in patients with IPAH. METHODS AND RESULTS: Patients with newly diagnosed IPAH who underwent symptom-limited cardiopulmonary exercise testing from November 11, 2010, to June 25, 2015, in our hospital were prospectively enrolled and followed for up to 66 months. Clinical worsening and mortality were recorded. A total of 210 patients with IPAH (159 women; mean age, 32±10 years) were studied with a median follow-up of 41 months. Thirty-one patients died, 1 patient underwent lung transplantation, and 85 patients presented with clinical worsening. The univariate analysis revealed that OUES, OUESI (OUESI=OUES/body surface area), peak oxygen uptake (V˙O2), peak V˙O2/kg, ventilation (V˙E)/carbon dioxide output (V˙CO2) slope, peak systolic blood pressure, heart rate recovery, pulmonary vascular resistance, cardiac index, N-terminal prohormone brain natriuretic peptide, and World Health Organization functional class were all predictive of clinical worsening and mortality (all P<0.05). Multivariate analysis demonstrated that OUESI and cardiac index were independently predictive of clinical worsening, and OUESI and N-terminal prohormone brain natriuretic peptide were independently predictive of mortality. Patients with OUESI ≤0.52 m-2 had a worse 5-year survival rate than patients with OUESI >0.52 m-2 (41.9% versus 89.8%, P<0.0001). CONCLUSIONS: The OUES, a submaximal parameter obtained from cardiopulmonary exercise testing, provides prognostic information for predicting clinical worsening and mortality in patients with IPAH.

Effect of calcium channel blockers evaluated by cardiopulmonary exercise testing in idiopathic pulmonary arterial hypertension responding to acute pulmonary vasoreactivity testing.

BACKGROUND: The baseline exercise capacity evaluated by cardiopulmonary exercise testing (CPET) and the change after administration of calcium channel blockers (CCB) therapy in patients with vasodilator-responsive idiopathic pulmonary arterial hypertension (VR-IPAH)are unknown. METHODS: 25 patients with newly diagnosed VR-IPAH from 1 January 2012 to 16 November 2015 were prospectively enrolled, and 28 age, sex and pulmonary vascular resistance matched newly diagnosed patients with vasodilator-nonresponsive idiopathic pulmonary arterial hypertension (VNR-IPAH) were enrolled. CPET was performed before and after 3.5 ± 0.8 months of CCB or sildenafil therapy. RESULTS: Ventilatory efficiency at rest, anaerobic threshold (AT), and peak were significantly higher (lower in V˙E/V˙CO2@AT and higher in PETCO2@AT) in VR-IPAH group than that in VNR-IPAH group. Peak V˙O2 (13.9 ± 2.9 mL kg-1·min-1 vs 16.4 ± 4.1 mL kg-1·min-1, p = 0.001), peak O2 pulse (5.5 ± 0.8 mL min-1·beat-1 vs 6.9 ± 1.3 mL min-1·beat-1, p = 0.001), V˙E/V˙CO2@AT (34.2 ± 5.0 vs 31.6 ± 3.1, p = 0.02) and PETCO2@AT (33.1 ± 4.0 mmHg vs 35.3 ± 3.2 mmHg, p = 0.02) were significantly improved after high dose of CCB therapy, along with improvement of WHO functional class, 6-min walking distance, NT-proBNP and tricuspid regurgitation pressure gradient. CONCLUSIONS: Ventilatory efficiency in patients with VR-IPAH is better than that in patients with VNR-IPAH. CCB can improve aerobic capacity and ventilatory efficiency during exercise in patients with VR-IPAH. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov:NCT02061787.

Predictors of Blood Pressure Fall With Continuous Positive Airway Pressure Treatment in Hypertension With Coronary Artery Disease and Obstructive Sleep Apnea.

BACKGROUND: The present study aimed to investigate the predictors of changes in blood pressure (BP) with continuous positive airway pressure (CPAP) treatment in hypertensive patients with coronary heart disease (CHD) and obstructive sleep apnea (OSA). METHODS: Seventy-one hypertensive patients with CHD and OSA were enrolled in this study. Daytime systolic BP (SBP), diastolic BP (DBP), Epworth Sleepiness Scale (ESS), and anthropometric characteristics were assessed at baseline and follow-up. RESULTS: Sixty-six patients completed the study. The median follow-up period was 36 months (interquartile range, 24-60 months). The mean duration of CPAP application was 4.3 ± 1.2 hours per night. From baseline to follow-up, SBP and DBP were reduced by 5.6 mm Hg (95% confidence interval [CI], 3.0-8.1) and 3.0 mm Hg (95% CI, 0.8-5.3), respectively. Daytime somnolence was significantly improved (ESS, from 9.5 ± 3.4 at baseline to 3.6 ± 2.0 at follow-up; P < 0.001); the mean improvement in ESS was 6.0 (95% CI, 5.1-6.9). Correlation analysis of the fall in mean BP (MBP) showed that baseline MBP, change in ESS, heart rate, and CPAP compliance showed a positive correlation, whereas the baseline body mass index (BMI) and ESS had an inverse relationship. Stepwise multiple linear regression analysis, however, indicated that only baseline BMI, baseline MBP, and CPAP compliance were independently correlated with the fall in MBP. CONCLUSIONS: Long-term CPAP treatment reduces BP in hypertensive patients with CHD and moderate/severe OSA; baseline BMI, baseline MBP, and CPAP compliance are independent predictors of the decrease in BP with CPAP treatment in these patients.

[Value of cardiopulmonary exercise testing in comparing cardio-pulmonary function among patients with three kinds of pulmonary artery hypertension].

OBJECTIVE: To assess the exercise capacity of three kinds of pulmonary artery hypertension using cardiopulmonary exercise testing (CPET). METHODS: In the Center for Pulmonary Vascular Disease Diagnosis and Treatment of Fuwai Hospital, idiopathic pulmonary artery hypertension (IPAH), congenital heart disease associated pulmonary artery hypertension (CHD-PAH), connective tissue disease associated pulmonary artery hypertension (CTD-PAH) were enrolled into this study from December 2012 to May 2013. CPET was performed in all patients, and clinical features, routine tests results, N-terminal B-type natriuretic peptide (NT-proBNP), Six-minutes-walk distance (6MWD) were all collected. RESULTS: Thirty-two patients with IPAH, 38 patients with CHD-PAH, 25 patients with CTD-PAH were enrolled. For IPAH, CHD-PAH, and CTD-PAH patients, the peak oxygen uptake via body weight (VO2max/kg) was (12.3 ± 2.3), (14.9 ± 4.0), and (11.1 ± 2.5) ml·min⁻¹·kg⁻¹, respectively. The peak VO2/kg was significantly different within these three groups (P<0.001), and was significantly higher in CHD-PAH patients compared with the other two groups (P=0.003, P<0.001). The peak VO2/heart rate (HR) was (5.8±1.4), (6.4 ± 1.8), (5.3 ± 1.7) ml·beat(-1)·min⁻¹ in the above three groups and was significantly different within these three groups (P=0.034). The peak VO2/HR was significantly increased in CHD-PAH patients than CTD-PAD patients (P=0.012). The peak HR was (136.1 ± 21.4), (140.8 ± 19.9), (124.5 ± 21.6) beat/min respectively and was significantly lower in CTD-PAD patients than CHD-PAH patients (P=0.009). The 6MWD was significantly decreased in CTD-PAD patients compared with CHD-PAH and IPAH patients (P=0.006, 0.010). Nt-proBNP was significantly decreased in CTD-PAD patients compared with CHD-PAH patients (P=0.012). In Pearson and partial correlation analysis, the peak VO2/kg was significantly correlated with peak VO2/HR, peak HR, 6MWD, Nt-proBNP, left ventricular end-diastolic diameter, right ventricular end-diastolic diameter (r=0.477, 0.518, 0.387, 0.465, -0.350, 0.349, -0.259). CONCLUSION: CPET parameters can objectively evaluate exercise capacity and cardiopulmonary function of the patients with pulmonary hypertension.

Long-term effects of continuous positive airway pressure on blood pressure and prognosis in hypertensive patients with coronary heart disease and obstructive sleep apnea: a randomized controlled trial.

BACKGROUND: Obstructive sleep apnea (OSA) can result in hypertension and significantly increase cardiovascular morbidity and mortality. There are few reports on the long-term effects of continuous positive airway pressure (CPAP) on blood pressure in patients with uncontrolled hypertension with coronary heart disease (CHD) and OSA. METHODS: We conducted a prospective, long-term follow-up study in 83 patients with uncontrolled hypertension, CHD, and OSA randomized to control or CPAP groups. Daytime systolic blood pressure (SBP), diastolic blood pressure (DBP), and severe cardiovascular and cerebrovascular events (SCCEs) were recorded at baseline and follow-up. RESULTS: Seventy-three patients completed the study with a median follow-up of 36 (interquartile range = 24-54) months. The 2 groups had similar characteristics at baseline. CPAP was used for 4.5±1.1 hour/night. SBP in the CPAP group was significantly reduced at follow-up (143±7 mm Hg vs. 139±7 mm Hg, P = 0.04), and SBP decreased by 8mm Hg (95% confidence interval = 1.4-9.9; P = 0.01). Hypertension control was improved (CPAP, 69.4% for CPAP users vs. 43.2% for control subjects; P = 0.02); however, DBP did not reach statistical difference between the groups (81±10 mm Hg vs. 79±8 mm Hg; P = 0.49). In the CPAP group, the Epworth Sleepiness Scale was markedly reduced (7.0±3.4 vs. 3.7±2.3; P < 0.001). There was 1 SCCE in the CPAP group (heart failure), and 5 SCCEs in the control group (acute myocardial infarction: 2 (with 1 death); stroke: 3), but there was no significant difference identified. CONCLUSIONS: Long-term CPAP application in uncontrolled hypertension with CHD and OSA significantly reduced daytime SBP, improved hypertension control and daytime sleepiness, and decreased the trend in SCCEs compared with control subjects. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02059993.

The lowest VE/VCO2 ratio best identifies chronic thromboembolic pulmonary hypertension.

INTRODUCTION: The natural history of acute pulmonary embolism (PE) under treatment is about a gradual resolution of the thrombi, and uncommonly, the development of chronic thromboembolic pulmonary hypertension (CTEPH). We hypothesized that ventilatory efficiency parameters during cardiopulmonary exercise testing (CPET) may be able to monitor the process and predict CTEPH. METHODS: 15 patients rehabilitated from acute PE (total resolution of thrombi), 44 patients with chronic PE (with residual thrombi), 66 patients with CTEPH, and 36 sedentary healthy controls performed incremental CPET. RESULTS: The lowest VE/VCO2 was higher in CTEPH patients than that in chronic PE and rehabilitated patients (43.4 L/min vs 29.9 L/min vs 27.1 L/min, p<0.005). The VE/VCO2 slope (48.4 L/min/L/min vs 29.9 L/min/L/min vs 28.0 L/min/L/min, p<0.005) and oxygen uptake efficiency plateau (OUEP) (37.1 L/min vs 27.0 L/min vs 25.2L/min, p<0.005) had the similar changes. In logistic regression analysis, the lowest VE/VCO2 ≥ 34.35 L/min was the best predictor of CTEPH (OR 159.0, 95% CI 36.0-702.3, p<0.001). The lowest VE/VCO2 was higher in chronic PE patients compared with the controls (29.9 L/min vs 26.5 L/min, p<0.05), but there was no difference between the rehabilitated patients and the controls. In multiple linear regression analysis, the percentage of vascular obstruction by ventilation-perfusion lung scanning (PVO) was the most significant independent predictor for indices of ventilatory efficiency in chronic PE and rehabilitated patients. CONCLUSIONS: CTEPH is associated with weakened ventilatory efficiency. The lowest VE/VCO2 ratio has the best capability to predict CTEPH. Ventilatory inefficiency improves along with recovery of acute PE.

[Value of cardiopulmonary exercise test in cardiac function evaluation of patients with chronic left heart failure caused by dilated cardiomyopathy].

OBJECTIVE: To assess the value of cardiopulmonary exercise test in the evaluation of cardiac function in patients with chronic left heart failure caused by dilated cardiomyopathy. METHODS: Fifty-three inpatients aged 18 year and over with chronic left heart failure caused by dilated cardiomyopathy at Fuwai Hospital from October 2010 to October 2011 were selected and divided into 2 groups according to the New York Heart Association (NYHA) heart function classification. One group had 20 cases for class II and another 33 cases for class III-IV. All of them received cardiopulmonary exercise tests. Synchronous measurement and record of gas exchange indices were taken during every breath, and so were heart rate, blood pressure, electrocardiogram and blood oxygen saturation. At the same time, other routine tests were also performed. After exercise test, anaerobic threshold and peak oxygen consumption indices were calculated and statistically analyzed. They also received subsequent follow-ups of 1 day, 1 week, 1 month, 6 months and 1 year, including activities, clinical manifestations and cardiac adverse events. RESULTS: At baseline, the differences in gender, age, body mass index, concurrent diseases, left ventricular end-diastolic diameter, left ventricular ejection fraction and serum creatinine had no statistical significance (P > 0.05). Compared with cardiac function class II group, the class III-IV group had higher left atrial diameter, level of amino terminal pro-B-type natriuretic peptide (NT-proBNP), incidence of atrial fibrillation ((51.4 ± 7.5) vs (43.6 ± 7.7) mm, (2 607 ± 1 782) vs (1 312 ± 901) µg/L, 42.4% (14/33) vs 5.0% (1/20)) and lower glomerular filtration rate, peak oxygen consumption, levels of anaerobic threshold ((72 ± 20) vs (97 ± 23) ml/min, (13.7 ± 2.6) vs (20.5 ± 3.6) ml·min(-1)·kg(-1), (10.7 ± 1.5) vs (13.3 ± 2.1) ml·min(-1)·kg(-1)) (all P < 0.01). And NT-proBNP and cardiac function classification showed a positive correlation (OR = 1.002, P = 0.003) while peak oxygen consumption, anaerobic threshold and cardiac function classification were negatively correlated (OR = 0.736, 0.608; P = 0.011, 0.001). CONCLUSIONS: Cardiopulmonary exercise test objectively reflects the cardiopulmonary reserve of heart failure patients with dilated cardiomyopathy. And the parameters of anaerobic threshold and peak oxygen consumption may reflect the patient's motor ability quantitatively and accurately.