Author + information
- Received September 21, 1994
- Revision received May 16, 1995
- Accepted May 24, 1995
- Published online October 1, 1995.
- Jan Brouwer, MDa,
- Dirk J. Van Veldhuisen, MD, FACCa,*,
- Arie J. Man In 't Veld, MDa,*,
- Peter H.J.M. Dunselman, MDa,†,
- Frans Boomsma, PhDa,*,
- Jaap Haaksma, BSca,
- K.I. Lie, MDa,
- For The Dutch Ibopamine Multicenter Trial (DIMT) Study Group
- ↵*Address for correspondence: Dr. Dirk J. van Veldhuisen. Department of Cardiology, Thoraxcenter, University Hospital Groningen, Oostcrsingcl 59, 9713 EZ Groningen, The Netherlands.
Objectives. This study assessed the effects of digoxin and ibopamine on variables of heart rate variability in relation to neurohormonal activation.
Background. Analysis of heart rate variability can be used to study the autonomic dysfunction that characterizes chronic heart failure. In the Dutch Ibopamine Multicenter Trial, patients with heart failure were found to have increased neurohormonal activation with placebo therapy but not with digoxin and ibopamine therapy.
Methods. We studied 59 patients with mild to moderate heart failure (mean [±SEM]age 60 ± 1 years, mean ejection fraction 0.30 ± 0.01). Patients were randomized to double-blind treatment with digoxin (0.25 mg [n = 22]), ibopamine (100 mg three times a day [n = 19]) or placebo (n = 18); background therapy consisted of furosemide (up to 80 mg).
Results. After 3 months, plasma norepinephrine levels had increased with placebo, whereas they decreased with digoxin (+31 vs. −60 pg/ml, respectively, p < 0.01). With ibopamine, a nonsig nificant decrease was observed (−27 pg/ml, p = 0.10). All variables of heart rate variability showed a deterioration in the placebo group. With digoxin, the percent differences between successive RR intervals >50 ms (pNN50) increased (+ 1.7 ± 0.9%, p < 0.01), along with absolute and normalized high frequency power (+40 ± 33 ms2, p < 0.05 and +2.4 ± 1.7%, p < 0.01, respectively). These changes were observed during daytime hours only and were most pronounced in patients with the most impaired baseline heart rate variability. With ibopamine, nonsignificant trends similar to the changes with digoxin were observed.
Conclusions. In patients with early stages of heart failure, digoxin may prevent a progressive deterioration in heart rate variability, whereas ibopamine does not show statistically significant effects. The changes in heart rate variability with digoxin parallel an observed decrease in neurohormonal activation. Digoxin apparently enhances cardiac vagal tone in the setting of neuroendocrine activation.
This study was presented in part at the 66th Annual Scientific Sessions of the American Heart Association, Atlanta, Georgia, November 1993. It was financially supported by a grant from Zambon Nederland B.V., a Division of the Zambon Group, Bresso, Milan, Italy. A list of the members of the DIMT Study Group and their affiliations appears in reference 18.
- Received September 21, 1994.
- Revision received May 16, 1995.
- Accepted May 24, 1995.
- American College of Cardiology