Bigyan Pudasaini

Comparative effectiveness of sildenafil for pulmonary hypertension due to left heart disease with HFrEF

There is no cure for pulmonary hypertension due to left heart disease (PH-LHD), but the rationale for using sildenafil to treat pulmonary arterial hypertension with heart failure with reduced ejection fraction (HFrEF) has been supported by short-term studies. We performed a meta-analysis to evaluate the effectiveness of sildenafil for PH-LHD with HFrEF. A systematic literature search of PubMed, EMBASE and the Cochrane Central Register of Controlled Trials was conducted from inception through October 2014 for randomized trials and for observational studies with control groups, evaluating the effectiveness of sildenafil to treat PH-LHD with HFrEF. Sildenafil therapy decreased pulmonary arterial systolic pressure both at the acute phase and at the 6-month follow-up (weighted mean difference (WMD): −6.03 mm Hg, P=0.02; WMD: −11.47 mm Hg, P<0.00001, respectively). Sildenafil was found to reduce mean pulmonary artery pressure (WMD: −3 mm Hg, P=0.0004) and pulmonary vascular resistance (WMD: −60.0 dynes cm−5, P=0.01) at the 3-month follow-up. Oxygen consumption at peak significantly increased to 3.66 ml min−1 kg−1 (P<0.00001), 3.36 ml min−1 kg−1 (P<0.00001) and 2.60 ml min−1 kg−1 (P=0.03) at 3, 6 and 12 months, respectively. There were significant reductions in ventilation to CO2 production slope of −2.00, −4.68 and −7.12 at 3, 6 and 12 months, respectively (P<0.00001). Sildenafil was superior to placebo regarding left ventricular ejection fraction at the 6-month follow-up (WMD: 4.35, P<0.00001), and it significantly improved quality of life. Sildenafil therapy could effectively improve pulmonary hemodynamics and cardiopulmonary exercise testing measurements of PH-LHD with HFrEF, regardless of acute or chronic treatment.

Exercise Training for Patients Pre- and Postsurgically Treated for Non–Small Cell Lung Cancer A Systematic Review and Meta-analysis

Background. This meta-analysis examined the effects of exercise training on length of hospital stay, postoperative complications, exercise capacity, 6-minute walking distance (6MWD), and health-related quality of life (HRQoL) in patients following resection of non–small cell lung cancer (NSCLC). Methods. This review searched PubMed, EMBASE, and the Cochrane Collaboration data base up to August 16, 2015. It includes 15 studies comparing exercise endurance and quality of life before versus after exercise training in patients undergoing lung resection for NSCLC. Results. This review identified 15 studies, 8 of which are randomized controlled trials including 350 patients. Preoperative exercise training shortened length of hospital stay; mean difference (MD): −4.98 days (95% CI = −6.22 to −3.74, P < .00001) and also decreased postoperative complications for which the odds ratio was 0.33 (95% CI = 0.15 to 0.74, P = .007). Four weeks of preoperative exercise training improved exercise capacity; 6MWD was increased to 39.95 m (95% CI = 5.31 to 74.6, P = .02) .While postoperative exercise training can also effectively improve exercise capacity, it required a longer training period; 6MWD was increased to 62.83 m (95% CI = 57.94 to 67.72) after 12 weeks of training (P < .00001). For HRQoL, on the EORTC-QLQ-30, there were no differences in patients’ global health after exercise, but dyspnea score was decreased −14.31 points (95% CI = −20.03 to −8.58, P < .00001). On the SF-36 score, physical health was better after exercise training (MD = 3 points, 95% CI = 0.81 to 5.2, P = .007) while there was no difference with regard to mental health. The I2 statistics of all statistically pooled data were lower than 30%. There was a low amount of heterogeneity among these studies. Conclusions. Evidence from this review suggests that preoperative exercise training may shorten length of hospital stay, decrease postoperative complications and increase 6MWD. Postoperative exercise training can also effectively improve both the 6MWD and quality of life in surgical patients with NSCLC, but requiring a longer training period.

Can we predict the prognosis of COPD with a routine blood test

Background The major characteristic of COPD is systemic inflammation. The parameters such as neutrophil-to-lymphocyte ratio (NLR) and eosinophil-to-basophil ratio (EBR) in routine blood test (RBT) are considered to be the underlying biomarkers of inflammation. We hypothesized that the prognosis of patients with COPD can be predicted with RBT. Methods Patients with COPD in stable stage were enrolled. The RBT, pulmonary function testing (PFT), BODE index, C-reactive protein (CRP), procalcitonin, and erythrocyte sedimentation rate (ESR) were performed at enrollment and every follow-up once in every 3 months during the 24-month follow-up period. Meanwhile, exacerbation count and mortality incidence were recorded. The correlation between the prognostic biomarkers and the prognosis of patients was analyzed. Results The NLR and EBR in RBT have a significant correlation with the severity of patients with COPD. The NLR is an independent predictor for mortality and the EBR is an independent predictor for exacerbation. Conclusion As an inexpensive, accessible, and convenient assay, RBT may be used as a practical means in the prediction of prognosis of patients with COPD in future clinical settings.

The relationship between tumor markers and pulmonary embolism in lung cancer

Background Tumor markers (TMs) and D-Dimer are both hallmarks of severity and prognosis of lung cancer. Tumor markers could be related to pulmonary embolism (PE) in lung cancer. Results The number of abnormal tumor markers of lung cancer patients with pulmonary embolism (3.9 ± 1.1vs1.6 ± 0.6,P 0.005) was more than that in patients without pulmonary embolism. TMs panel (P trend < 0.001), CEA (R2 0.735, P0.003) and CYFRA21-1 (R2 0.718, P0.005) were positively correlated with D-Dimer in patients with pulmonary embolism. The multivariate logistic regression analysis showed that, for tumor markers, TMs panel (OR5.98, P < 0.001) had the strongest correlation with pulmonary embolism. The AUC (area under curve) of TMs panel and CEA were 0.82 [95%CI (0.71–0.95), P < 0.001] and 0.71 [95%CI (0.62–0.84), P 0.002] by ROC (receiver operating characteristic) curve analysis, respectively. Materials and Methods Tumor markers were compared between lung cancer patients complicated with pulmonary embolism and those without pulmonary embolism Then the correlation between each tumor marker as well as panel of combined TMs and D-Dimer as well as pulmonary embolism were analyzed for patients with pulmonary embolism. Conclusions There is a relationship between tumor markers and pulmonary embolism in patients with lung cancer. The panel of combined tumor markers is a valuable diagnostic marker for pulmonary embolism in lung cancer.

Cardiopulmonary exercise testing improves diagnostic specificity in patients with echocardiography‐suspected pulmonary hypertension

Doppler echocardiography is usually the first diagnostic investigation for patients suspected with pulmonary hypertension (PH), but it is often inaccurate when used alone, especially in mild PH.

The Correlation of Decreased Heart Rate Recovery and Chronotropic Incompetence with Exercise Capacity in Idiopathic Pulmonary Arterial Hypertension Patients

We show by this study that a decrease in HRR1 in IPAH patients is associated with severe limitation of exercise capacity. HRR1 < 16 beats and CI just after completion of a CPET could be an indicator of poor prognosis.

Oxygen Uptake Efficiency Slope, an Objective Submaximal Parameter in Evaluating Exercise Capacity in Pulmonary Thromboembolism☆☆☆☆☆☆

Objective: The objective of this article was to study the oxygen uptake efficiency, an index of cardiopulmonary functional reserve that can be based upon a submaximal exercise effort, in pulmonary thromboembolism (PE) by performing the cardiopulmonary exercise test. Materials and Methods: The cardiopulmonary exercise test with simultaneous respiratory gas measurement was performed in 50 patients with PE and in 50 healthy individuals. All subjects also underwent the pulmonary function test. Peak oxygen uptake (peak VO2), anaerobic threshold (AT), oxygen uptake efficiency slope (OUES), oxygen uptake efficiency plateau (OUEP) and oxygen uptake efficiency at anaerobic threshold (OUE@AT), were determined. Results: (1) Compared with the controls, the patients with PE had lower peak VO2, AT, OUES, OUEP and OUE@AT (P < 0.001). (2) In patients with PE, oxygen uptake efficiency (OUE = VO2/VE) at warming up, AT and peak exercise but not rest, were indicated statistically lower than the controls. The OUE in normal subjects increased as unloaded exercise began, and then increased further to OUEP just before the AT. Thereafter, the OUE decreased gradually until peak exercise. In contrast, the rate of changes of the OUE in patients with PE was relatively mild during exercise. (3) Of all the submaximal parameters, OUES correlated best with peak VO2 (r = 0.712, P < 0.001). Conclusions: The oxygen uptake efficiency of patients with PE was lower than the controls during exercise. The OUE is an objective measure of cardiopulmonary reserve that does not require a maximal exercise effort. Therefore, OUES could be helpful to assess exercise performance in patients with PE who are unable to perform a maximal exercise test in early recovery stage.

Transition from Ambrisentan to Bosentan in Pulmonary Arterial Hypertension: A Single-Center Prospective Study

Background and objective: Two endothelin receptor antagonists (ETRAs), bosentan and ambrisentan, are approved for patients with pulmonary arterial hypertension (PAH). However, there is little information about the transition strategy between these two ETRAs. We aimed to evaluate the safety and efficacy from ambrisentan to bosentan. Methods: Twenty PAH patients were enrolled into the single-center, open-labelled prospective study. Echocardiogram, WHO functional class (WHO-FC), 6-minute walking distance (6MWD), right heart catheterization, and hemotology were collected. After receiving oral 5 mg ambrisentan daily initially for one year, the patients were divided into two arms: eight patients switched to bosentan, while the remaining 12 patients continued ambrisentan. Characteristics at baseline, 1-and 2-year follow-up points were compared. Results: There were no significant differences in echocardiogram, WHO-FC, hemodynamics, demographics and liver function at baseline, 1-and 2-year points in both arms. 6MWD in bosentan group was significantly shorter at baseline. But there were no significant differences of 6MWD at 1- and 2-year points. Conclusions: It is safe for stable PAH patients to transition from ambrisentan to bosentan without hemodynamic or hematologic deterioration.

Sex-specific cardiopulmonary exercise testing indices related to hemodynamics in idiopathic pulmonary arterial hypertension.

Background: Many studies have highlighted sex preponderance in idiopathic pulmonary arterial hypertension (IPAH). It is well established that there are differences in exercise capacities in the two sexes but how much of that difference reflects on disease severity or correlates to markers of severity in the two sexes is still not clear. Right heart catheterization (RHC) and cardiopulmonary exercise testing (CPET) have been widely used for assessing functional capacity, prognosis and treatment response in IPAH. We aimed to investigate the ‘sex-specific’ CPET parameters in relation to hemodynamics in IPAH. Methods: Data were retrieved from 30 males and 53 females [mean ± standard deviation (SD) age: 39.6 ± 17.2 and 37.5 ± 12.0] stable IPAH patients who underwent both RHC and CPET at Shanghai Pulmonary Hospital from 2010 to 2016. Univariate and forward/backward multiple stepwise regression analysis was performed to assess the prognostic value of CPET and hemodynamic parameters. Results: There were no significant differences in clinical variables between men and women. Peak workload, peak oxygen uptake, anaerobic threshold (AT), peak minute ventilation, carbon dioxide output, O2 pulse and oxygen uptake efficiency slope were significantly higher in men compared with women (p < 0.05). Several CPET indexes correlated with hemodynamics. Pulmonary vascular resistance (PVR) and cardiac output (CO) were distinctly different between the sexes. Peak end-tidal partial pressure of CO2 (PETCO2) was an independent predictor of PVR elevation in all patients and in men. Peak maximum oxygen consumption (VO2) was independently predictive of CO decline in all patients and in men. Only peak O2 pulse was an independent predictor of increased PVR and decreased CO in women. Conclusions: Even after adjusting for age, body mass index and World Health Organization functional class, different CPET parameters correlated with PVR elevation and CO decline in men and women differently, which could potentially better predict severity in men and women with IPAH.

Sex-specific cardiopulmonary exercise testing indices to estimate the severity of inoperable chronic thromboembolic pulmonary hypertension

Background Sex differences in chronic thromboembolic pulmonary hypertension (CTEPH) have been revealed in few studies. Although right heart catheterization (RHC) is the gold standard for clinical diagnosis and assessment of prognosis in pulmonary hypertension (PH), cardiopulmonary exercise testing (CPET) has been a more widely used assessment of functional capacity, disease severity, prognosis, and treatment response in PH. We hypothesized that the “sex-specific” CPET indices could estimate the severity of inoperable CTEPH. Methods Data were retrieved for 33 male (age, mean ± standard deviation [SD] =62.5±13.4 years) and 40 female (age, mean ± SD =56.3±11.8 years) patients with stable CTEPH who underwent both RHC and CPET at Shanghai Pulmonary Hospital from February 2010 to February 2016. Univariate and forward/backward multiple stepwise regression analysis was performed to assess the predictive value of CPET indices to hemodynamic parameters. Event-free survival was estimated using the Kaplan–Meier method and analyzed with the log-rank test. Cox proportional hazards models were performed to determine the independent event-free survival predictors. Results Numerous CPET parameters were different between male and female patients with CTEPH and the control group. There were no significant differences in both clinical variables and RHC parameters between male and female patients with CTEPH. O2 pulse, workload, minute ventilation (VE), and end-tidal partial pressure of O2 (PETO2) at anaerobic threshold, as well as peak O2 pulse, workload, VE, and nadir VE/CO2 were significantly higher in male patients than in female patients (P<0.05). Only oxygen uptake efficiency plateau (OUEP) showed a significantly higher difference in female than male patients (P<0.05). In addition, several CPET indices correlated with hemodynamic parameters, especially pulmonary vascular resistance (PVR), which was distinctly different between the sexes. Nadir VE/CO2 was an independent predictor of PVR in male patients with CTEPH, whereas OUEP was an independent predictor of PVR in female patients with CTEPH. Conclusion Even after confounding for age and body mass index, different CPET measurements of gas exchange efficiency correlated with PVR differently between male and female patients. This potentially could be used to estimate the severity of CTEPH.