PURPOSE: To review the nature and multi-dimensional aspects of fatigue in several different disease states and to develop a preliminary conceptualization of the nature of fatigue in PAH. To suggest aspects of fatigue that should be evaluated in PAH patients.
METHODS: Broad systematic review of the PAH literature. Search terms used were “PAH”, “quality of life”, and “patient reported outcomes”, and “fatigue”. Results were synthesized and consistent trends identified. The PAH literature is reviewed in order to develop a working conceptual model of the dimensions of fatigue previously noted in PAH
RESULTS: Fatigue is a key patient symptom in PAH, a potential marker for disease progression and may be predictive of patient deterioration. Review of the literature surrounding fatigue in other disease states, notably undifferentiated cancer, breast cancer, chronic fatigue syndrome, and HIV make clear that fatigue in each of these disease states is a multi-dimensional construct. General fatigue has been shown to be distinguishable between fatigue associated with direct physical limitations such as oxygenation/perfusion due to cardiac inefficiency, fatigue resulting as a consequence of insomnia or of challenges of sleep loss, fatigue associated with the symptoms of depression or as a consequence of anxiety, and fatigue arising as a consequence of the burdens imposed by therapy or insufficient rest due to medications.
CONCLUSIONS: Fatigue in PAH is a multi-dimensional construct, involving fatigue arising as a consequence of inadequate cardiac efficiency, inadequate or un-restful sleep, and as a consequence of anxiety or depression.
CLINICAL IMPLICATIONS: Development of a conceptual model of fatigue in PAH and its impact on patients is a first, necessary step in the systematic quantification of fatigue in this population. Understanding the different forms and causes of patient fatigue will enhance the clinician’s understanding of the impact of the disease and treatment on the PAH patient’s quality of life.
DISCLOSURE: Matthew Murawski: Consultant fee, speaker bureau, advisory committee, etc.: Mattthew Murawski serves as a consultant to Pfizer,Inc
Robert Frantz: Grant monies (from industry related sources): Pfizer: Consulting fees,United Therapeutics: Served on advisory boards without personal financial gain. but with coverage of travel expense. Received research support. Received educational grants., Consultant fee, speaker bureau, advisory committee, etc.: Actelion: Served on advisory boards without personal financial gain but with coverage of travel expense.. Received educational grants.Gilead: Served on advisory boards without personal financial gain, but with coverage of travel expense., Other: Bayer: Consulting to develop educational program with them; my institution received the fees in keeping with Mayo COI policy for investigators.
Mardi Gomberg-Maitland: Grant monies (from industry related sources): Actelion, Gilead, Lilly/Icos, Pfizer, Novartis, and United Therapeutics have provided funding to the University of Chicago to support Dr. Gomberg-Maitland’s conduct of clinical trials., Consultant fee, speaker bureau, advisory committee, etc.: She has served as a consultant/participant on data safety monitoring board/steering committee for clinical trials for Actelion, Drais, Gilead, Medtronic, and Pfizer.
Hubert Chen: Grant monies (from industry related sources): Pfizer,Inc, Consultant fee, speaker bureau, advisory committee, etc.: United Therapeutics, Consultant fee, speaker bureau, advisory committee, etc.: Genentech
Joel Fain: Employee: Pfizer,Inc
James Cwengros: Employee: Pfizer,Inc
Kafi Sanders: Employee: Pfizer,Inc
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