Morphological abnormalities in baseline ECGs in healthy normal volunteers participating in phase I studies.

BACKGROUND & OBJECTIVES: Morphological abnormalities in 12-lead electrocardiograms (ECGs) are seen in subgroups of healthy individuals like athletes and air-force personnel. As these populations may not truly represent healthy individuals, we assessed morphological abnormalities in ECG in healthy volunteers participating in phase I studies, who are screened to exclude associated conditions.

METHODS

ECGs from 62 phase I studies analyzed in a central ECG laboratory were pooled. A single drug-free baseline ECG from each subject was reviewed by experienced cardiologists. ECG intervals were measured on five consecutive beats and morphological abnormalities identified using standard guidelines.

RESULTS

Morphological abnormalities were detected in 25.5 per cent of 3978 healthy volunteers (2495 males, 1483 females; aged 18-76 yr); the presence was higher in males (29.3% vs. 19.2% in females; P<0.001). Rhythm abnormalities were the commonest (11.5%) followed by conduction abnormalities (5.9%), axis deviation (4%), ST-T wave changes (3.1%) and chamber enlargement (1.4%). Incomplete right bundle branch block (RBBB), short PR interval and right ventricular hypertrophy were common in young subjects (<20 yr) while atrial fibrillation, first degree atrioventricular block, complete RBBB and left anterior fascicular block were more prevalent in elderly subjects (>65 yr). Prolonged PR interval, RBBB and intraventricular conduction defects were more common in males while sinus tachycardia, short PR interval and non-specific T wave changes were more frequent in females.

INTERPRETATION & CONCLUSIONS: Morphological abnormalities in ECG are commonly seen in healthy volunteers participating in phase I studies; and vary with age and gender. Further studies are required to determine whether these abnormalities persist or if some of these disappear on follow up.