Materials and Methods
Eligible participants :
Female individuals diagnosed with ME/CFS, who underwent HUT at Stichting CardioZorg between November 2014 and April 2018 because of a clinical suspicion of orthostatic intolerance (OI), and in whom a complete set of the PPT’s pre- and post-HUT was available, were included in this study. Male patients were not studied because of differences in PPT values compared to female patients. ME/CFS was considered present if participants met both the 1994 International Chronic Fatigue Syndrome Study Group criteria for CFS(29) and the 2011 international consensus definition of ME(30), taking the exclusion criteria into account. During the first visit ME/CFS patients were classified as having FM or not. FM was considered present when the diagnosis had been confirmed in the past by a rheumatologist or when patients fulfilled the criteria of FM based on the American College of Rheumatology (ACR) fibromyalgia questionnaire(31). For comparison 22 healthy female subjects underwent the same test.
The study was carried out in accordance with the Declaration of Helsinki. The use of clinical data for descriptive studies (PT1450) and the use of HC (P1411) was approved by the ethics committee of the Slotervaart Hospital, the Netherlands. All patients gave informed consent.
Head-up tilt table test :
The HUT was performed as described previously(32). Briefly, testing was conducted at least 3 hours after a light meal. Participants were encouraged to ingest an ample amount of fluid on the day of the procedure, but did not drink fluids in the 2 hours before the test. Participants were studied in a climate-controlled room where the temperatures ranged from 22-24⁰ C. Individuals were studied in the supine position for 15 minutes, and for 30 minutes in the upright position (70-degrees). The test was ended after 30 minutes, at the request of the patient, or if the individual developed syncope or pre-syncope.
Heart rate (HR), systolic and diastolic blood pressures (SBP and DBP) were continuously recorded by finger plethysmography using the Nexfin device (BMeye, Amsterdam, NL)(33, 34). An independent radio-controlled clock was used to mark the starting time of HR and BP recordings as well as the time of the start of tilting. HR and BP data were extracted from the Nexfin device and imported into an Excel spreadsheet. Supine HR and BP data were calculated from the last minute before tilting. Upright HR and BP data were calculated from the last minute of the upright position, and referred to as the end of study (EOS) values. Nasal prongs were placed to measure expired carbon dioxide (CO2) concentrations. For the tilt testing component, individuals being treated with medication that could alter HR or BP (beta-adrenergic antagonists, midodrine, fludrocortisone, desmopressin, pyridostigmine bromide, anti-hypertensive medications, or ivabradine) were excluded from this analysis. Individuals being treated with selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors continued to take these medications. Patients using neuropathic pain medication (opioids, anti-depressants, anti-epileptics, low dose naltrexone) were also allowed to continue the medication.