Masaharu Kataoka

Percutaneous Transluminal Pulmonary Angioplasty for the Treatment of Chronic Thromboembolic Pulmonary Hypertension

Background—Chronic thromboembolic pulmonary hypertension leads to pulmonary hypertension and right-sided heart failure. The purpose of this study was to investigate the efficacy of percutaneous transluminal pulmonary angioplasty (PTPA) for the treatment of chronic thromboembolic pulmonary hypertension. Methods and Results—Twenty-nine patients with chronic thromboembolic pulmonary hypertension underwent PTPA. One patient had a wiring perforation as a complication of PTPA and died 2 days after the procedure. In the remaining 28 patients, PTPA did not produce immediate hemodynamic improvement at the time of the procedure. However, after follow-up (6.0 ± 6.9 months), New York Heart Association functional classifications and levels of plasma B-type natriuretic peptide significantly improved (both P<0.01). Hemodynamic parameters also significantly improved (mean pulmonary arterial pressure, 45.3 ± 9.8 versus 31.8 ± 10.0 mm Hg; cardiac output, 3.6 ± 1.2 versus 4.6 ± 1.7 L/min, baseline versus follow-up, respectively; both P<0.01). Twenty-seven of 51 procedures in total (53%), and 19 of 28 first procedures (68%), had reperfusion pulmonary edema as the chief complication. Patients with severe clinical signs and/or severe hemodynamics at baseline had a high risk of reperfusion pulmonary edema. Conclusions—PTPA improved subjective symptoms and objective variables, including pulmonary hemodynamics. PTPA may be a promising therapeutic strategy for the treatment of chronic thromboembolic pulmonary hypertension. Clinical Trial Registration—URL: http://www.umin.ac.jp. Unique identifier: UMIN000001572.

Human Pentraxin 3 (PTX3) as a Novel Biomarker for the Diagnosis of Pulmonary Arterial Hypertension

Background Although inflammation is an important feature of pulmonary arterial hypertension (PAH), the usefulness of local inflammatory markers as biomarkers for PAH is unknown. In this study, we tested whether plasma concentrations of human pentraxin 3 (PTX3), a local inflammatory marker, would be a useful biomarker for detecting PAH. Methods Plasma PTX3 concentrations were evaluated in 50 PAH patients (27 with idiopathic PAH, 17 with PAH associated with connective tissue disease (CTD-PAH), and six with congenital heart disease), 100 age and sex-matched healthy controls, and 34 disease-matched CTD patients without PAH. Plasma concentrations of B-type natriuretic peptide (BNP) and C-reactive protein (CRP) were also determined. Results Mean PTX3 levels were significantly higher in all PAH patients than in the healthy controls (4.40±0.37 vs. 1.94±0.09 ng/mL, respectively; P<0.001). Using a threshold level of 2.84 ng/mL, PTX3 yielded a sensitivity of 74.0% and a specificity of 84.0% for the detection of PAH. In CTD-PAH patients, mean PTX3 concentrations were significantly higher than in CTD patients without PAH (5.02±0.69 vs. 2.40±0.14 ng/mL, respectively; P<0.001). There was no significant correlation between plasma levels of PTX3 and BNP or CRP. Receiver operating characteristic (ROC) curves for screening PAH in patients with CTD revealed that PTX3 (area under the ROC curve 0.866) is superior to BNP. Using a PTX3 threshold of 2.85 ng/mL maximized true-positive and false-negative results (sensitivity 94.1%, specificity 73.5%). Conclusion Plasma concentrations of PTX3 may be a better biomarker of PAH than BNP, especially in patients with CTD.

Efficacy of 360-degree three-dimensional rotational pulmonary angiography to guide percutaneous transluminal pulmonary angioplasty

Percutaneous transluminal pulmonary angioplasty (PTPA) is performed with balloon dilatation of the target lesions in the pulmonary arteries through a catheter (Online Figure 1A-Online Figure 1C, Moving image 1, Moving image 2). We routinely perform pulmonary angiography (PAG) using a rotational digital angiography system (Artis zeego multi-axis; Siemens AG, Forchheim, Germany) before the PTPA procedure (Moving image 3). A 360-degree three-dimensional (3D) PAG image is used for identifying the target lesions and estimating their perfusion area easily and rapidly, in addition to identifying the anatomical structures of the pulmonary arteries (Figure 1A, Moving image 4). A rotational 3D PAG image can help us develop therapeutic strategies during PTPA procedures, including guide catheter and balloon size selection. Furthermore, we can visualise the pulmonary artery anatomy in synchronisation with the realtime angiographic view during the procedure, resulting in safe and easy wiring. The rotational 3D PAG image after PTPA is shown in Figure 1B and Moving image 5. Accordingly, this rotational 3D PAG image contributes to the safe and easy performance of PTPA and reduces the amount of contrast agent, leading to a reduction in radiation exposure.

Sorafenib as a potential strategy for refractory pulmonary arterial hypertension

Sorafenib is an inhibitor of multi-kinases including tyrosine and serine/threonine kinases. We investigated the efficacy and safety of sorafenib for the treatment of patients with refractory pulmonary arterial hypertension (PAH). Sorafenib was started in 9 patients (7 with idiopathic PAH, 2 with pulmonary veno-occlusive disease) who had severe PAH and right heart failure, in spite of treatment with vasodilators specific for PAH. Sorafenib was started as an add-on therapy at a dose of 50 or 100xa0mg/day, and increased to 100-400xa0mg/day. New York Heart Association functional class improved in 8 patients and did not change in 1. Mean pulmonary arterial pressure improved in 6 patients (14-28% decrease) and did not apparently change in 2 (follow-up catheterization was not performed in 1 patient). The main adverse effects of sorafenib were skin reactions on the hands and feet, which appeared in 5 patients. They were tolerable in 4 patients, but discontinuation of sorafenib was needed in only 1 patient. In conclusion, sorafenib had favorable effects to improve symptoms and objective variables in patients with refractory PAH, with tolerable adverse events. Sorafenib is an alternative strategy for patients with refractory PAH.

Arterial methemoglobin level predicts therapeutic effectiveness of the PDE5 inhibitors in patients with in idiopathic pulmonary arterial hypertension.

Background The PDE5 inhibitors are emerging as novel therapeutic tools in patients with idiopathic pulmonary arterial hypertension (PAH). However, the response to the PDE5 inhibitors varies among patients. The PDE inhibitor augments and prolongs the vasodilator effect of NO. Thus, therapeutic effectiveness of the PDE inhibitors relies on the ability of pulmonary vascular endothelial cells to produce NO. Hemoglobin binds to NO with great affinity and forms methemglobin by oxidation in the erythrocyte. We hypothesized that methemoglobin level is correlated positively with the capacity of NO production in pulmonary vascular endothelial cells and can be used as a biomarker for prediction of therapeutic response to the PDE5 inhibitors.