Effect of dual pulmonary vasodilator therapy in pulmonary arterial hypertension associated with congenital heart disease: a retrospective analysis

Background: Patients with pulmonary arterial hypertension (PAH) are managed according to evidence-based treatment guidelines. Methods and results: In this single-centre retrospective analysis, we examined outcomes of patients with PAH caused by congenital heart disease (PAH-CHD) with respect to exercise capacity and survival of adults treated with either bosentan or sildenafil monotherapy or bosentan-sildenafil dual therapy between January 2007 and January 2014. Of the 82 patients analysed, 29 had Down syndrome; 54 (65.8%) received bosentan monotherapy, 16 (19.5%) sildenafil monotherapy and 12 (14.6%) dual therapy. Mean treatment duration was 2.5 years for all patients and 4.1 years for 38 patients treated for ≥2 years. Pooled patient and treatment data showed initial improvement followed by stabilisation in mean 6 min walk distance (6MWD). For Down and non-Down patients, mean 6MWD increased and then stabilised on bosentan monotherapy. Mean 6MWD of patients on dual therapy at the time of analysis was 246.3 m before PAH-specific therapy initiation, 211.9 m immediately prior to addition of a second therapy and 214.4 m at last visit while on dual therapy. 1, 2 and 3- year survival rates for all patients from time of treatment initiation were 96%, 87% and 80%, respectively. Conclusions: For the majority of patients, monotherapy with a PAH-specific medication provided improved and sustained exercise benefits. For the small percentage of patients who required it, add-on therapy appeared to prevent further deterioration in exercise capacity but did not improve 6MWD

Effect of tungsten doping on the properties of In2O3 films.

Highly crystalline tungsten oxide (WO3)-doped indium oxide (In2O3) films are synthesized at room temperature by the RF magnetron sputtering technique. The structural and morphological properties of the as-deposited films and the films annealed at a temperature of 300°C are investigated in detail. X-ray diffraction analysis reveals the presence of a cubic bixbyite structure with preferred orientation along the (222) plane for both the as-deposited and annealed films. Moderate WO3 doping (1 wt.%) enhances the crystallinity of the as-deposited In2O3 films, whereas the crystallinity of the films systematically decreases with an increase in WO3 doping concentration beyond 1 wt.%. Raman spectral analysis discloses the modes of the cubic bixbyite In2O3 phase in the films. Atomic force microscopy micrographs show a smooth and dense distribution of smaller grains in the films. X-ray photoelectron spectroscopy reveals the existence of W5+ in the doped films. The undoped film is highly oxygen deficient. Variation in the concentration of oxygen vacancy can be associated with the degree of crystallinity of the films

Highly ordered good crystalline ZnO-doped WO3 thin films suitable for optoelectronic applications.

Highly ordered ZnO-doped WO3 thin films with good crystalline quality are prepared using radio frequency magnetron sputtering technique, and its morphological and structural properties are studied using various characterization tools such as field emission scanning electron microscopy, energy-dispersive x-ray spectroscopy, x-ray diffraction technique, micro-Raman spectroscopy, and x-ray photoelectron spectroscopy. Morphological analysis shows a smooth surface for pure film, whereas the ZnO-doped films presents a dense distribution of grains of larger sizes with well-defined grain boundary. X-ray diffraction studies reveal the enhancement of crystalline quality of the films with increase in ZnO doping concentration up to 5 wt.%, beyond which the crystalline quality gets deteriorated. A phase modification from a single monoclinic WO3 phase to mixed monoclinic WO3 and W18O49 phases is observed for films with higher ZnO doping concentrations

Study on the structural, morphological and optical properties of RF-sputtered dysprosium-doped barium tungstate thin films.

Barium tungstate films with different Dy3+ doping concentrations, namely 0 wt.%, 1 wt.%, 3 wt.% and 5 wt.%, are deposited on cleaned quartz substrate by radio frequency magnetron sputtering technique and the prepared films are annealed at a temperature of 700{deg}C. The structural, morphological and optical properties of the annealed films are studied using techniques such as x-ray diffraction (XRD), micro-Raman spectroscopy, field emission scanning electron microscopy, atomic force microscopy and photoluminescence spectroscopy. XRD analysis shows that all the films are well-crystallized in nature with a monoclinic barium tungstate phase. The presence of characteristic modes of the tungstate group in the Raman spectra supports the formation of the barium tungstate phase in the films. Scanning electron microscopic images of the films present a uniform dense distribution of well-defined grains with different sizes. All the doped films present a broad emission in the 390-500 nm region and its intensity increases up to 3 wt.% and thereafter decreases due to usual concentration quenching

Rationale, design and methodology of APPROACH-IS II: International study of patient-reported outcomes and frailty phenotyping in adults with congenital heart disease.

In recent years, patient-reported outcomes (PROs) have received increasing prominence in cardiovascular research and clinical care. An understanding of the variability and global experience of PROs in adults with congenital heart disease (CHD), however, is still lacking. Moreover, information on epidemiological characteristics and the frailty phenotype of older adults with CHD is minimal. The APPROACH-IS II study was established to address these knowledge gaps. This paper presents the design and methodology of APPROACH-IS II. APPROACH-IS II is a cross-sectional global multicentric study that includes Part 1 (assessing PROs) and Part 2 (investigating the frailty phenotype of older adults). With 53 participating centers, located in 32 countries across six continents, the aim is to enroll 8000 patients with CHD. In Part 1, self-report surveys are used to collect data on PROs (e.g., quality of life, perceived health, depressive symptoms, autonomy support), and explanatory variables (e.g., social support, stigma, illness identity, empowerment). In Part 2, the cognitive functioning and frailty phenotype of older adults are measured using validated assessments. APPROACH-IS II will generate a rich dataset representing the international experience of individuals in adult CHD care. The results of this project will provide a global view of PROs and the frailty phenotype of adults with CHD and will thereby address important knowledge gaps. Undoubtedly, the project will contribute to the overarching aim of improving optimal living and care provision for adults with CHD

Internal mammary artery smooth muscle cells resist migration and possess high antioxidant capacity

Objective- This study investigated whether differences exist in atherogen-induced migratory behaviors and basal antioxidant enzyme capacity of vascular smooth muscle cells (VSMC) from human coronary (CA) and internal mammary (IMA) arteries. Methods- Migration experiments were performed using the Dunn chemotaxis chamber. The prooxidant [NAD(P)H oxidase] and antioxidant [NOS, superoxide dismutase, catalase and glutathione peroxidase] enzyme activities were determined by specific assays. Results- Chemotaxis experiments revealed that while both sets of VSMC migrated towards platelet-derived growth factor-BB (1-50 ng/ml) and angiotensin II (1-50 nM), neither oxidized-LDL (ox-LDL, 25-100 �g/ml) nor native LDL (100 �g/ml) affected chemotaxis in IMA VSMC. However, high dose ox-LDL produced significant chemotaxis in CA VSMC that was inhibited by pravastatin (100 nM), mevastatin (10 nM), losartan (10 nM), enalapril (1 �M), and MnTBAP (a free radical scavenger, 50��M). Microinjection experiments with isoprenoids i.e. geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate (FPP) showed distinct involvement of small GTPases in atherogen-induced VSMC migration. Significant increases in antioxidant enzyme activities and nitrite production along with marked decreases in NAD(P)H oxidase activity and O2 .- levels were determined in IMA versus CA VSMC. Conclusions- Enhanced intrinsic antioxidant capacity may confer on IMA VSMC resistance to migration against atherogenic agents. Drugs that regulate ox-LDL or angiotensin II levels also exert antimigratory effects