Cardiac Autonomic Functioning is Impaired Among Allogeneic Hematopoietic Stem Cell Transplantation Survivors: a Controlled Study

Healthy cardiac autonomic functioning (CAF) is essential for maintaining homeostasis in response to the environmental demands of everyday life. Impaired CAF is associated with higher morbidity and higher mortality. To explore CAF in survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) 1-10 years after transplant (median=4.3 years), an ambulatory assessment was performed with 104 patients, and 45 age- and gender-matched healthy controls. Heart rate (HR) and respiratory sinus arrhythmia (RSA, that is, high-frequency HR variability) were measured in a laboratory setting and during a 12-hour naturalistic period of daily life. Cancer-related fatigue was assessed by the Functional Assessment of Chronic Illness - Fatigue questionnaire; physical fitness by bicycle-ergometry VOmax. In contrast to healthy controls, 4-year post-HSCT fatigue was greater in patients (P<0.0001, Cohen's d effect size [d]=1.14), and fitness was lower in patients (P<0.0001, d=1.09). In both laboratory and real-life ambulatory conditions, average HR was persistently higher (P<0.0001, d=0.88) and mean RSA magnitude lower (P<0.001, d=0.69) among patients, compared with controls. Severely fatigued patients showed higher HR and lower parasympathetic cardiac control than non-fatigued patients (HR: P=0.02, d=0.47; RSA: P=0.02, d=0.72), and this was unrelated to fitness. These findings may have important implications for predicting long-term treatment outcome and consequences for routine post-HSCT care.