Postural orthostatic tachycardia syndrome in adolescents with ME/CFS - a case control study.

Introduction: Postural orthostatic tachycardia syndrome (PoTS) can be associated with myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS). Pediatric PoTS requires a "sustained" rise in orthostatic heart rate ≥40 bpm above supine heart rate (relative limit), often >120 bpm (absolute limit). However, the diagnostic criteria for PoTS in adolescents remain underexplored, particularly regarding the definition of "sustained" tachycardia, which poses challenges in clinical and research settings. This study examined orthostatic intolerance criteria, including PoTS, in adolescents with ME/CFS and healthy controls. Methods: Medical history of orthostatic intolerance was assessed by a semi-structured interview with 18 ME/CFS patients and 18 matched healthy controls (14-17 years). A passive 10-min standing test with minute-by-minute heart rate and blood pressure registration was performed. PoTS was diagnosed by a clinical expert based on current consensus criteria. Data were analyzed using Fisher's exact test and receiver operating characteristic analysis. Results: Although history of orthostatic intolerance was positive in 15/18 ME/CFS [83%, 0.95 CI (61; 94)] and 3/18 healthy controls [17%, 0.95 CI (5.9; 39)], PoTS was diagnosed in only 7/18 ME/CFS [39%, 0.95 CI (20; 61)] vs. no healthy controls [0%, 0.95 CI (0; 18)]. Subgroups were identified, e.g., positive history of orthostatic intolerance yet physiological passive 10-min standing test, or negative history of orthostatic intolerance yet tachycardia in passive 10-minute standing test. PoTS diagnosis by the clinical expert matched best with the passive 10-min standing test alone when at least 60% of upright heart rate values were above one or both limits. The absolute limit was superior to the relative limit in distinguishing adolescents with and without PoTS. Discussion: PoTS was observed only in ME/CFS. In adolescents with ME/CFS, positive history of orthostatic intolerance, along with at least 60% of heart rate values above published upright-position limits, may allow non-experts to make a valid diagnosis, facilitating clinical care and future studies. Further research will show if these results can be generalized.