Increased exercise ejection fraction and reversed remodeling after long-term treatment with metoprolol in congestive heart failure: a randomized, stratified, double-blind, placebo-controlled trial in mild to moderate heart failure due to ischemic or idiopathic dilated cardiomyopathy.
BACKGROUND
the effects of long-term administration of beta-blockers on left ventricular (LV) function during exercise in patients with ischemic heart disease (IHD) and idiopathic dilated cardiomyopathy (DCM) are controversial.


METHODS
patients with stable congestive heart failure (CHF) (New York heart association [NYHA] class II and III) and ejection fraction (EF) < or =0.40 were randomized to metoprolol, 50 mg t.i.d. or placebo for 6 months. Patients were divided into two groups: ischemic heart disease (IHD) and idiopathic dilated cardiomyopathy (DCM). The mean EF was 0.29 in both groups and 92% were taking angiotensin-converting enzyme (ACE) inhibitors. In the IHD group, 84% had suffered a myocardial infarction (MI) and 64% had undergone revascularization at least 6 months before the study. LV volumes were measured by equilibrium radionuclide angiography. Mitral regurgitation was assessed by Doppler echocardiography. All values are changes for metoprolol subtracted by changes for placebo.


RESULTS
metoprolol improved LV function markedly both at rest and during sub-maximal exercise in both groups. The mean increase in EF was 0.069 at rest (P<0.001) and 0.078 during submaximal exercise (P<0.001). LV end-diastolic volume decreased by 22 ml at rest (P=0.006) and by 15 ml during exercise (P=0.006). LV end-systolic volume decreased by 23 ml both at rest (P=0.001) and during exercise (P=0.004). Exercise time increased by 39 s (P=0.08). In the metoprolol group, mitral regurgitation decreased (P=0.0026) and only one patient developed atrial fibrillation vs. eight in the placebo group (P=0.01).


CONCLUSIONS
metoprolol improves EF both at rest and during submaximal exercise and prevents LV dilatation in mild to moderate CHF due to IHD or DCM.
Waagstein
F
F
Wallenberg Laboratory and Department of Cardiology, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. Waagstein@wlab.gu.se
Strömblad
O
O
Andersson
B
B
Böhm
M
M
Darius
M
M
Delius
W
W
Goss
F
F
Osterziel
K J
KJ
Sigmund
M
M
Trenkwalder
S-P
SP
Wahlqvist
I
I
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D002311:Cardiomyopathy, Dilated / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology; D005080:Exercise Test; D005260:Female; D015637:Gated Blood-Pool Imaging; D006321:Heart / Q000000981:diagnostic imaging; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000627:therapeutic use*; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D013318:Stroke Volume / Q000502:physiology*; D013997:Time Factors; D020257:Ventricular Remodeling / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D008790:Metoprolol