September 12, 2003

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

FWFinn WaagsteinHeart Failure & Transplant OSO. StrömbladSahlgrenska University Hospital BABert AnderssonHeart Failure & Transplant

Structured PICO

Does metoprolol improve left ventricular function at rest and during exercise in patients with mild to moderate congestive heart failure?

Population

Patients with stable congestive heart failure (NYHA class II and III) and ejection fraction ≤0.40 due to ischemic heart disease (IHD) or idiopathic dilated cardiomyopathy (DCM).

Intervention

Metoprolol 50 mg t.i.d. for 6 months

Comparator

Matching placebo for 6 months

Outcome

Left ventricular function (ejection fraction and LV volumes) at rest and during sub-maximal exercise at 6 monthssurrogate

Long-term metoprolol treatment improves ejection fraction and reverses left ventricular remodeling both at rest and during exercise in patients with mild to moderate heart failure.

Abstract

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. PATIENTS AND 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). CONCLUSION: metoprolol improves EF both at rest and during submaximal exercise and prevents LV dilatation in mild to moderate CHF due to IHD or DCM.

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