QTc interval and its variability in patients with schizophrenia and healthy subjects: implications for a thorough QT study.
We compared heart rate-corrected QT interval (QTc) and its within- and between-subject variability, in ECGs recorded several days apart for 207 patients with schizophrenia (age range 19-60 yr) with age- and gender-matched healthy controls. Patients had higher heart rates (mean±s.d.) than controls [75±15 beats per minute (bpm) vs. 63±10 bpm; p<0.0001]. QTc by Bazett's formula (QTcB) overestimated QTc interval at high heart rates; consequently QTcB was longer in patients (412±24 ms) than in controls (404±24 ms; p=0.0003). QTc by Fridericia's method (QTcF), which was not influenced by heart rate, was comparable (398±22 ms in patients vs. 401±19 ms in controls; p=0.17). Between-subject variability in QTcF was similar in patients (17 ms) and controls (16.2 ms) but within-subject variability was larger (13.1 ms vs. 10 ms, respectively). Thus, a larger sample size is required when thorough QTc studies with a cross-over design are performed in patients with schizophrenia than in healthy subjects; sample size is not increased for studies with a parallel design. Last, QTcF is preferred over QTcB in schizophrenia patients with higher heart rates.
Research Section, Quintiles Cardiac Safety Services, Mumbai, India. Pooja.hingorani@quintiles.com
Pooja
P
Hingorani
Dilip R
DR
Karnad
Mili
M
Natekar
Snehal
S
Kothari
Dhiraj
D
Narula
Yash
Y
Lokhandwala
D000328:Adult; D016022:Case-Control Studies; D004562:Electrocardiography / Q000379:methods*; D005260:Female; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000453:epidemiology / Q000503:physiopathology*; D055815:Young Adult