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.