Electrocardiographic reference ranges derived from 79,743 ambulatory subjects.
BACKGROUND
Reference ranges for electrocardiogram (ECG) intervals, heart rate, and QRS axis in general use by medical personnel and ECG readers are unrepresentative of true age- and sex-related values in large populations and are not based on modern electrocardiographic and ECG reading technology.


RESULTS
The results of ECG interpretation by cardiologists using digital technology for viewing and interpreting ECGs were compiled from single, baseline ECGs of 79,743 individuals included in pharmaceutical company-sponsored clinical trials. Women comprised 48% of the total population. Ages ranged from 3 months to 99 years, and the bulk of the population (56%) was aged 40 to 70 years. Striking differences in numerical ECG values based on age and sex were observed. A subgroup of 46,129 individuals with a very low probability of cardiovascular disease was identified. The following were the reference ranges for this subgroup, determined using the 2nd and 98th percentiles: heart rate, 48 to 98 beats/min; PR interval, 113 to 212 milliseconds; QRS interval, 69 to 109 milliseconds; frontal plane QRS axis, -40 degrees to 91 degrees ; QT interval, 325 to 452 milliseconds; QTc-Bazett, 361 to 457 milliseconds; and QTc-Fridericia, 359 to 445 milliseconds. There were marked age- and sex-related variations in the reference ranges of this subgroup, and they differ substantially from previously reported norms. Small differences were observed in ECG values obtained using our digital methods as compared with readings done using paper tracings and values computed by 2 commercial computer algorithms.


CONCLUSIONS
We observed large differences in electrocardiographic heart rate, interval, and axis reference ranges in this study compared with those reported previously and with reference ranges in general use. We also observed a large influence of age and sex upon normal values. Very large cohorts are required to fully assess age- and sex-related variation of reference ranges. Electrocardiographic reference ranges should be modernized.
Mason
Jay W
JW
Covance Cardiac Safety Services, Inc, Reno, NV 89521, USA. jay.mason@covance.com
Ramseth
Douglas J
DJ
Chanter
Dennis O
DO
Moon
Thomas E
TE
Goodman
Daniel B
DB
Mendzelevski
Boaz
B
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D015716:Electrocardiography, Ambulatory / Q000592:standards* / Q000706:statistics & numerical data*; D005260:Female; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009505:Nevada / Q000453:epidemiology; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017678:Sex Distribution