American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Feb 2024
Implications of Mean Pulmonary Arterial Wedge Pressure Trajectories in Pulmonary Arterial Hypertension.
Rationale: The mean pulmonary arterial wedge pressure (mPAWP) is the critical hemodynamic factor differentiating group 1 pulmonary arterial hypertension (PAH) from group 2 pulmonary hypertension associated with left heart disease. Despite the discrepancy between the mPAWP upper physiologic normal and current PAH definitions, the implications of the initial mPAWP for PAH clinical trajectory are poorly understood. Objectives: To model longitudinal mPAWP trajectories in PAH over 10 years and examine the clinical and hemodynamic factors associated with trajectory membership. ⋯ An mPAWP-high trajectory was associated with shorter transplant-free survival (vs. mPAWP-low, median, 7.8 vs. 11.3 yr; log-rank P = 0.017; age-adjusted P = 0.217). Conclusions: Over 10 years, the mPAWP followed two distinct trajectories, with 25% evolving into group 2 pulmonary hypertension physiology. Using routine baseline data, longitudinal mPAWP trajectory could be predicted accurately, with initial mPAWP ⩾12 mm Hg as one of the strongest predictors.
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Am. J. Respir. Crit. Care Med. · Feb 2024
ReviewElexacaftor/Tezacaftor/Ivacaftor Treatment and Depression-related Events.
Rationale: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) has been shown to be safe and efficacious in people with cystic fibrosis (pwCF) aged 2 years and older with at least one F508del-CFTR allele or more. After U. S. approval in 2019, reports emerged of depression-related adverse events in pwCF treated with ELX/TEZ/IVA. ⋯ Data from CF registries in the United States and Germany showed that patterns of depression prevalence in pwCF exposed to ELX/TEZ/IVA did not change after treatment initiation. Published studies utilizing the nine-item Patient Health Questionnaire did not show evidence of worsening depression symptoms in pwCF treated with ELX/TEZ/IVA. Conclusions: Our review of data from clinical trials, postmarketing reports, an ongoing registry-based ELX/TEZ/IVA postauthorization safety study, and peer-reviewed literature suggests that depression symptoms and depression-related events reported in pwCF treated with ELX/TEZ/IVA are generally consistent with background epidemiology of these events in the CF population and do not suggest a causal relationship with ELX/TEZ/IVA treatment.