Selej, Mona

ABSTRACTThere is a need for objective, continuous and remote assessment of exercise capacity in patients with pulmonary arterial hypertension (PAH). Using data from the TRACE study, in which 108 adult patients with PAH were continuously monitored with a wrist‐worn accelerometer, we evaluated whether actigraphy can facilitate continuous monitoring of exercise capacity. Distributions of step rate, distance and duration of patient's walking bouts were estimated at baseline, Week 16 and Week 24 using 2‐week periods of actigraphy data. Twenty‐one metrics per walking bout characteristic were described (mean, standard deviation, 19 percentiles [5th–95th]). The relationships between these metrics and the 6‐min walk distance (6MWD), Borg dyspnea index (BDI), and the PAH Symptoms and Impact questionnaire (PAH‐SYMPACT) Physical Impact domain score were assessed at the three timepoints. Test‐retest reliability, and discriminant and known‐group validity of each metric were also evaluated. All metrics of step rate and bout distance were significantly correlated with 6MWD (Pearson's correlation coefficients: 0.34–0.67; p < 0.005) and the PAH‐SYMPACT Physical Impact domain score (Pearson's correlation coefficients: −0.51 to −0.32; p < 0.05) at all timepoints. Negative correlations were also observed with the BDI and the actigraphy‐derived metrics, with the majority reaching significance. Strong test‐retest reliability was demonstrated (intra‐class correlation coefficient ≥ 0.70). The metrics differentiated well between patients with varying disease severity levels. In conclusion, actigraphy‐derived metrics of patients' walking bouts correlate significantly with 6MWD, BDI and physical impacts of PAH, indicating the utility of actigraphy in facilitating continuous monitoring of exercise capacity in adult patients with PAH.Trial RegistrationClinicalTrials.gov: NCT03078907; URL: clinicaltrials.gov.

AbstractMacitentan is a dual endothelin receptor antagonist (ERA) approved for treating pulmonary arterial hypertension (PAH). SOPRANO evaluated the efficacy and safety of macitentan versus placebo in pulmonary hypertension (PH) patients after left ventricular assist device (LVAD) implantation. SOPRANO was a phase 2, multicenter, double‐blind, randomized, placebo‐controlled, parallel‐group study. Patients with an LVAD implanted within the prior 90 days who had persistent PH (i.e., mean pulmonary arterial pressure ≥25 mmHg, pulmonary artery wedge pressure [PAWP] ≤18 mmHg, and pulmonary vascular resistance [PVR] >3 Wood units [WU]) were randomized (1:1) to macitentan 10 mg or placebo once daily for 12 weeks. The primary endpoint was change in PVR. Secondary endpoints included change in right‐heart catheterization hemodynamic variables, N‐terminal prohormone of brain natriuretic peptide levels, World Health Organization functional class, and safety/tolerability. Fifty‐seven patients were randomized to macitentan (n = 28) or placebo (n = 29). A statistically significant reduction in PVR from baseline to Week 12 was observed with macitentan versus placebo (placebo‐corrected geometric mean ratio, 0.74; 95% confidence interval, 0.58–0.94; p = .0158). No statistically significant differences were observed in secondary endpoints. In a post‐hoc analysis, 66.7% of patients receiving macitentan achieved PVR <3 WU versus 40.0% receiving placebo (p = .0383). Macitentan was generally well tolerated; adverse events were consistent with those in previous PAH studies with macitentan. In conclusion, macitentan showed promising tolerability and significantly reduced PVR in PH patients with persistently elevated PVR after LVAD implantation. ClinicalTrials. gov identifier: NCT02554903.