Cardiac electrophysiologic monitoring after injection of gadobenate dimeglumine versus placebo in healthy volunteers and patients with cardiovascular disease.
OBJECTIVE
To prospectively compare intraindividual effects of 0.2 mmol/kg gadobenate dimeglumine and placebo (saline) on cardiac electrophysiology in healthy volunteers and patients with coronary artery disease (CAD).


METHODS
Gadobenate dimeglumine and saline placebo were injected intravenously approximately 72 hours apart in randomized crossover fashion in 24 healthy volunteers and 23 patients with CAD. Twelve-lead ambulatory (Holter) electrocardiographic (ECG) monitoring was performed from 3 hours preinjection to 24 hours postinjection. Quantitative and qualitative evaluation was performed with automated algorithmic interpretations and blinded assessment by one cardiologist. Possible QT-interval prolongation was evaluated after correction for heart rate on an individualized basis and by means of Bazett formula. Statistical analyses based on two-sided confidence intervals (CIs) were performed by using a linear model for a two-period crossover design. All subjects were monitored for vital signs, laboratory variables, and adverse events.


RESULTS
Placebo was administered before contrast agent in 12 volunteers and 12 patients and after contrast agent in 12 volunteers and 11 patients. For mean increase in QTc interval from baseline, a nonsignificant difference of 3.1 msec was noted between gadobenate dimeglumine and placebo (95% CI: -1.8, 8.0) after individualized correction. Overcorrection for heart rate was noted with Bazett formula (mean difference, 5.6 msec; 95% CI: -2.2, 13.5). Cardiologist findings were consistent with automated readings. Similar findings were noted for healthy volunteers and patients with CAD. No differences between treatments were noted for any evaluation, although more frequent qualitative changes were noted in patients with CAD. Adverse events were noted in seven of 47 (15%) subjects after gadobenate dimeglumine injection and in five of 47 (11%) subjects after injection of placebo.


CONCLUSIONS
Injection of 0.2 mmol/kg gadobenate dimeglumine has no detrimental effect on cardiac electrophysiology or other safety parameters in healthy volunteers or patients with CAD.
Pirovano
Gianpaolo
G
Worldwide Medical Affairs, Bracco Diagnostics, Princeton, NJ, USA.
Goodman
Daniel B
DB
Halemane
Usha
U
Venetianer
Carole
C
Kirchin
Miles A
MA
Spinazzi
Alberto
A
D000293:Adolescent; D000328:Adult; D003287:Contrast Media / Q000009:adverse effects*; D003327:Coronary Disease / Q000503:physiopathology*; D018592:Cross-Over Studies; D015716:Electrocardiography, Ambulatory; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008536:Meglumine / Q000008:administration & dosage / Q000009:adverse effects* / Q000031:analogs & derivatives*; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D011446:Prospective Studies
D003287:Contrast Media; D009942:Organometallic Compounds; C064572:gadobenic acid; D008536:Meglumine