Author + information
- Christophe Meune, MD and
- Denis Duboc, MD, PhD⁎ ()
- ↵⁎Department of Cardiology, Cochin Hospital, 27 rue du Fg St-Jacques, 75014 Paris, France
We thank Drs. Stöllberger and Finsterer for their comments about our paper (1). They point out several questions, indicating that they probably do not adhere to our conclusion of a preventive effect of perindopril in children with Duchenne muscular dystrophy. The main limitation may be the apparent delay of 60 months to observe a benefit of therapeutics.
In fact, this trial investigated a preventive effect very early in the course of Duchenne disease (mean age of children 10.6 years with normal left ventricular ejection fraction [LVEF]); as a consequence, LVEF was preserved at 36 months. These children probably have cardiac involvement that is not accurately detected by conventional measurements; more sensitive methods might be useful in this setting (2). Conversely, after 60 months’ total follow-up, children were older (mean age 15.6 years) and cardiac deterioration could be demonstrated in the group receiving placebo during phase 1; this is in accordance with the natural course of the disease. Such degradation in LVEF is representative of the ineluctable course of the disease, and it was not accurately prevented by a delayed initiation of perindopril. As 1) groups were comparable for demographics, cardiac status, respiratory and peripheral muscle function, 2) drug allocation (placebo or perindopril) during phase 1 was the only difference, thus the natural conclusion is that five years of perindopril may delay the onset and progression of LV dysfunction when compared to later and shorter initiation. The trend in lower mortality in the perindopril group reinforces our conclusion.
All adverse effects mentioned in our study were present during the first phase of the study, with no difference between placebo group or perindopril group.
Patients with and without LVEF dysfunction at the end of the protocol had similar baseline values (64.9 ± 6.5% vs. 65.0 ± 5.4%, respectively, p = NS).
No patient had significant increased LVEF during the study. Mean LVEF declined moderately in both groups, and some patients exhibited more severe degradation, which reflects heterogeneity in the course of the disease.
In our study, radionuclide ventriculography was chosen to determine LVEF, as it is the “gold standard” method. The measurement of LVEF is a direct count of radionuclide activity. Conversely, LVEF determined by echocardiography needs a mathematical hypothesis that may not be valid in cases of severe thoracic deformation (3). Finally, patients with Duchenne disease very frequently have poor quality of acoustic echocardiographic windows.
This study was focused on a possible preventive effect of perindopril on LVEF, which is an important prognosis factor, contrary to electrocardiograms, ventricular arrhythmias, and late potential signal-average (4).
In conclusion, this correspondence illustrates the need for simple and adequate methodology to limit misinterpretation of investigative results, integrating the difficulties of such necessary controlled trials conducted in a rare disease.
- American College of Cardiology Foundation
- Duboc D.,
- Meune C.,
- Lerebours G.,
- DeJaux J.Y.,
- Vaksmann G.,
- Becane H.M.
- Meune C.,
- Pascal O.,
- Bécane H.M.,
- et al.
- Chambers J.W.,
- duCret R.P.,
- Bowers T.R.,
- Engeler C.E.,
- Bache R.J.,
- Haidet G.C.