Interventional and pharmacological management of chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by obstruction of the pulmonary vasculature, leading to increased pulmonary vascular resistance and ultimately right ventricular failure, the leading cause of death in non-operated patients. This article reviews the current management of CTEPH. The standard of care in CTEPH is pulmonary endarterectomy (PEA). However, up to 40% of patients with CTEPH are ineligible for PEA, and up to 51% develop persistent/recurrent PH after PEA. Riociguat is currently the only medical therapy licensed for treatment of inoperable or persistent/recurrent CTEPH after PEA based on the results of the Phase III CHEST-1 study. Studies of balloon pulmonary angioplasty (BPA) have shown benefits in patients with inoperable or persistent/recurrent CTEPH after PEA; however, data are lacking from large, prospective, controlled studies. Studies of macitentan in patients with inoperable CTEPH and treprostinil in patients with inoperable or persistent/recurrent CTEPH showed positive results. Combination therapy is under evaluation in CTEPH, and long-term data are not available. In the future, CTEPH may be managed by PEA, medical therapy or BPA - alone or in combination, according to individual patient needs. Patients should be referred to experienced centers capable of assessing and delivering all options

Determination of viscoelastic properties of dates (Mazafati Variety)

The knowledge of rheological properties of agricultural fruits can be significantlyhelpful in design and fabrication of the appropriateprocessing machines .In this study, the viscoelastic characteristics of date (Mazafati variety) were investigated. Experimental tests were established in six moisture levels (7.5, 9.0, 10.8, 12.8, 17.59 and 25.5 on dry basis) and temperature of 45ºC which contributed to obtain a suitable model. To achieve the desired moisture levels, various saturated salts were used. A chamber capable of controlling temperature was fabricated and placed around the plunger of texture analyzer to monitor the temperature during the experiments. Tests were conducted using an Instron Universal Testing Machine in the way that, samples were exposed to a sudden load of 1.7 Newton for 300 seconds. Experimental data of creep tests were fitted into Burger four-element model. Results indicated that, creep factor inclines when moisture content increases, meanwhile, its minimum and maximum values were 0.08 mm and 0.26 mm at the moisture contents of 7.5% d.b. and 25.5% d.b., respectively. Consequently, constant values related to the model, were determined and correlated with moisture contents of products using non-linear regression analysis. Analysis of variances and using Tuky test (Pvalue<0.01) on creep parameters revealed that moisture content has significant effect on all firmness values except primary strain. Moreover, the moisture content showed a great impact on delay time. According to the results, rheological properties of date are highly dependent on its moisture content

Repetative Transcranial Magnetic Stimulator (rTMS) Characterization and How to Develop the Functionalities for Treating Neural Disorders

Background: Repetative transcranial magnetic stimulation (rTMS) is an important non-invasive technique with several protocols to treat a wide variety of neural disorders. This method utilizes a strong power supply to discharge high currents in a single or dual flat spiral coil with specific characterizations. It makes a magnetic field that promotes neuroplasticity by applying the field distribution on the appropriate brain zone and requires adjusting time and frequency relating to intervention protocols. Aim: This study investigates components of an rTMS machine to describe development approaches to increase performance, specifically in the binary mode of recovering proportionally with brain and heart signals. Methods: The proposed method achieves an rTMS and probe-set coil prototypes whose performance is approved with some statistical modelings and experiments analysis. Results: Results show that the physical properties of the coil are proportional to the power supply effect and the magnetic field distribution in front of the probe set. Conclusion: By clarifying the mechanism of oscillator switching modes and the location of the processing unit in rTMS, this paper is directed to utilize external sensors to create a smart stimulator with touch EEG or ECG signals through the most accurate intervention

An Open-source Image Analysis Toolbox for Quantitative Retinal Optical Coherence Tomography Angiography

Background: Qualitative and quantitative assessment of retinal perfusion using optical coherence tomography angiography (OCTA) has shown to be effective in the treatment and management of various retinal and optic nerve diseases. However, manual analyses of OCTA images to calculate metrics related to Foveal Avascular Zone (FAZ) morphology, and retinal vascular density and morphology are costly, time-consuming, subject to human error, and are exposed to both inter and intra operator variability.Objective: This study aimed to develop an open-source software framework for quantitative OCTA (QOCTA). Particularly, for analyzing OCTA images and measuring several indices describing microvascular morphology, vessel morphology, and FAZ morphology.Material and Methods: In this analytical study, we developed a toolbox or QOCTA using image processing algorithms provided in MATLAB. The software automatically determines FAZ and measures several parameters related to both size and shape of FAZ including area, perimeter, Feret’s diameter circularity, axial ratio, roundness, and solidity. The microvascular structure is derived from the processed image to estimate the vessel density (VD). To assess the reliability of the software, three independent operators measured the mentioned parameters for the eyes of 21 subjects. The consistency of the values was assessed using the intraclass correlation coefficient (ICC) index.Results: Excellent consistency was observed between the measurements completed for the superficial layer, ICC >0.9. For the deep layer, good reliability in the measurements was achieved, ICC >0.7. Conclusion: The developed software is reliable; hence, it can facilitate quantitative OCTA, further statistical comparison in cohort OCTA studies, and can assist with obtaining deeper insights into retinal variations in various populations

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits and collated via case report forms. Results: In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial [CHEST-2]). Conclusion: Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified

Use of clinically relevant responder threshold criteria to evaluate the response to treatment in the Phase III PATENT-1 study

Abstract BACKGROUND: In PATENT-1, riociguat significantly improved 6-minute walking distance (6MWD) and a range of secondary end-points in patients with pulmonary arterial hypertension (PAH). We investigated whether riociguat increased the proportion of patients achieving clinically relevant responder thresholds compared with placebo during PATENT-1. METHODS: In PATENT-1, a randomized, double-blind study, treatment-naïve patients or patients on background PAH-targeted therapy with symptomatic PAH received 12 weeks of treatment with placebo, riociguat up to 2.5 mg 3 times daily, or riociguat up to 1.5 mg 3 times daily. Increases in 6MWD ≥40 m, 6MWD ≥380 m, cardiac index ≥2.5 liter/min/m(2), mixed venous oxygen saturation ≥65%, World Health Organization functional class I/II, N-terminal pro-brain natriuretic peptide <1,800 pg/ml, and right atrial pressure <8 mm Hg were chosen as threshold criteria of a positive response. RESULTS: Riociguat increased the proportion of treatment-naïve patients and patients on background PAH-targeted therapy with 6MWD ≥380 m at Week 12 (+21% and +15%, respectively), whereas there was a small reduction in 6MWD in placebo-treated patients for both sub-groups. Riociguat also increased the proportion of treatment-naïve patients and patients on background PAH-targeted therapy achieving World Health Organization functional class I/II (+12% and +19%, respectively) and cardiac index ≥2.5 liter/min/m(2) (+30% and +33%, respectively) at Week 12, whereas there was little change in the respective placebo groups. CONCLUSIONS: Compared with placebo, riociguat increased the proportion of treatment-naïve patients and patients on background PAH-targeted therapy who fulfilled criteria defining a positive response to therapy

Incidence and prognostic significance of malignant arrhythmias during (repetitive) Holter electrocardiograms in patients with pulmonary hypertension

BackgroundIn patients with pulmonary hypertension (PH), increased pulmonary vascular resistance (PVR) may lead to increased right ventricular afterload and cardiac remodelling, potentially providing the substrate for ventricular arrhythmias. Studies dealing with long term monitoring of patients with PH are rare. The present study evaluated the incidence and the types of arrhythmias retrospectively recorded by Holter ECG in patients with newly detected PH during a long-term Holter ECG follow-up. Moreover, their impact on patient survival was evaluated.Patients and methodsMedical records were screened for demographic data, aetiology of PH, incidence of coronary heart disease, level of brain natriuretic peptide (BNP), results from Holter ECG monitoring, 6-minute walk test distance, echocardiographic data and hemodynamic data derived from right heart catheterization. Two subgroups were analyzed: 1. patients (n = 65) with PH (group 1 + 4) and derivation of at least 1 Holter ECG within 12 months from initial detection of PH and 2. patients (all PH etiologies, n = 59) with 3 follow-up Holter ECGs. The frequency and complexity of premature ventricular contractions (PVC) was classified into “lower” and “higher” (=non sustained ventricular tachycardia, nsVT) burden.ResultsHolter ECG revealed sinus rhythm (SR) in most of the patients (n = 60). Incidence of atrial fibrillation (AFib) was low (n = 4). Patients with premature atrial contractions (PAC) tend to have a shorter period of survival (p = 0.098), PVC were not correlated with significant survival differences. During follow-up PAC and PVC were common in all PH groups. Holter ECG revealed non sustained ventricular tachycardia in 19/59 patients [(32.2%); n = 6 during first Holter-ECG, n = 13 during second/third Holter-ECG]. In all patients suffering from nsVT during follow-up previous Holter ECG revealed multiform/repetitive PVC. PVC burden was not linked to differences in systolic pulmonary arterial pressure, right atrial pressure, brain natriuretic peptide and results of six-minute walk test.ConclusionPatients with PAC tend to have a shortened survival. None of the evaluated parameters (BNP, TAPSE, sPAP) was correlated with the development of arrhythmias. Patients with multiform/repetitive PVC seem to be at risk for ventricular arrhythmias