title: Heart Rate Variability for Early Detection of Cardiac Iron Deposition in Patients with Transfusion-Dependent Thalassemia.
abstract: BACKGROUND
  Iron overload cardiomyopathy remains the major cause of death in patients with transfusion-dependent thalassemia. Cardiac T2* magnetic resonance imaging is costly yet effective in detecting cardiac iron accumulation in the heart. Heart rate variability (HRV) has been used to evaluate cardiac autonomic function and is depressed in cases of thalassemia. We evaluated whether HRV could be used as an indicator for early identification of cardiac iron deposition.
  
  
  METHODS
  One hundred and one patients with transfusion-dependent thalassemia were enrolled in this study. The correlation between recorded HRV and hemoglobin, non-transferrin bound iron (NTBI), serum ferritin and cardiac T2* were evaluated.
  
  
  RESULTS
  The median age was 18 years (range 8-59 years). The patient group with a 5-year mean serum ferritin >5,000 ng/mL included significantly more homozygous β-thalassemia and splenectomized patients, had lower hemoglobin levels, and had more cardiac iron deposit than all other groups. Anemia strongly influenced all domains of HRV. After adjusting for anemia, neither serum ferritin nor NTBI impacted the HRV. However cardiac T2* was an independent predictor of HRV, even after adjusting for anemia. For receiver operative characteristic (ROC) curve analysis of cardiac T2* ≤20 ms, only mean ferritin in the last 12 months and the average of the standard deviation of all R-R intervals for all five-minute segments in the 24-hour recording were predictors for cardiac T2* ≤20 ms, with area under the ROC curve of 0.961 (p<0.0001) and 0.701 (p = 0.05), respectively.
  
  
  CONCLUSIONS
  Hemoglobin and cardiac T2* as significant predictors for HRV indicate that anemia and cardiac iron deposition result in cardiac autonomic imbalance. The mean ferritin in the last 12 months could be useful as the best indicator for further evaluation of cardiac risk. The ability of serum ferritin to predict cardiac risk is stronger than observed in other thalassemia cohorts. HRV might be a stronger predictor of cardiac iron in study populations with lower somatic iron burdens and greater prevalence of cardiac iron deposition.
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Suchaya
authors.initials: S
authors.lastname: Silvilairat
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Pimlak
authors.initials: P
authors.lastname: Charoenkwan
authors.affiliation: Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.|Biomedical Engineering Center, Faculty of Engineering, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Suwit
authors.initials: S
authors.lastname: Saekho
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Adisak
authors.initials: A
authors.lastname: Tantiworawit
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Arintaya
authors.initials: A
authors.lastname: Phrommintikul
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Somdet
authors.initials: S
authors.lastname: Srichairatanakool
authors.affiliation: Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.|Center of Excellence in Cardiac Electrophysiology Research, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Nipon
authors.initials: N
authors.lastname: Chattipakorn
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D042241:Early Diagnosis; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006339:Heart Rate; D006801:Humans; D019190:Iron Overload / Q000175:diagnosis* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D065227:Transfusion Reaction; D055815:Young Adult; D017086:beta-Thalassemia / Q000628:therapy*