European Heart Journal (1992) 13, 1217-1224
Muscle energy metabolism in severe chronic congestive heart failure — effect of treatment with enalapril M. BROQVIST*, U. DAHLSTROM*, E. KARLSSON* AND J. LARSSONI
From the Departments of * Cardiology and f Surgery, University of Health Sciences, Linkoping, Sweden KEY WORDS: Chronic heart failure, energy metabolism, enalapril, healthy individuals, muscle. Bv using biopsies, skeletal muscle metabolism was investigated in 22 patients with severe chronic heart failure. All the patients were in New York Heart Association functional class IV and constituted a subgroup of the previously published CONSENSUS trial. After this initial investigation ofmuscle metabolism in patients with chronic heartfailure, the influence of the angiotensin converting enzyme inhibitor, enalapril, on skeletal muscle metabolism was studied by randomizing the patients in a doubleblind manner to receive either placebo (n = 11) or enalapril (n=ll) in addition to conventional treatment. At the time of inclusion, the muscle content of energy-rich compounds, i.e. glycogen and the high energy phosphates, adenosine triphosphate (A TP) and phosphocrea tine, was reduced as compared with healthy subjects and muscle lactate content tended to be higher than normal. Following study treatment, no significant changes occurred, neither within nor between the two subgroups. Thus, patients with severe chronic congestive heart failure display metabolic derangement in muscle, which, in this study, was not corrected by treatment with enalapril. Introduction Exertional fatigue is frequently present in patients with congestive heart failure (CHF) but the correlations between cardiac function and exercise tolerance are weak'11. These findings have focused interest on the role of peripheral factors which limit exercise. Previous studies have revealed abnormal skeletal muscle metabolism during exercise in patients with CHF which might be due to inadequate blood flow1'-21. Angiotensin converting enzyme (ACE) inhibitors have vasodilating properties and have been shown to increase exercise tolerance in patients with heart failure131. The present investigation was conducted to examine skeletal muscle metabolism at rest in patients with severe chronic heart failure who have symptoms at rest (New York Heart Association functional class IV) and compare it to the situation in healthy individuals. We were also interested in investigating whether the addition of an ACE inhibitor (enalapril) to the conventional treatment with digitalis and diuretics might alter the skeletal muscle metabolism. Materials and methods PATIENTS
This study was performed in 22 patients participating in the CONSENSUS trial, which was a randomized, doubleblind, placebo-controlled, parallel-group trial studying the effects of enalapril on mortality in patients with severe congestive heart failure (CHF) New York Heart Association (NYHA) functional class IV14'. Because of a considerable reduction in mortality in the patients treated Submitted for publication on 15 July 1991, and in revised form 3 February 1992. Correspondence- Macs Broqvist, MD, Department of Cardiology, University Hospital, S-581 85 Linkoping, Sweden. 0195-66SX/92/091217 + 08 $08.00/0
with enalapril the CONSENSUS trial was discontinued ahead of schedule as recommended by the Ethical Review Committee141. The diagnosis of CHF was based on clinical criteria: a history of heart disease with symptoms of dyspnoea or fatigue or both, together with signs of fluid retention (pulmonary venous congestion, distended neck veins, hepatomegaly or peripheral oedema) and no evidence of primary pulmonary disease. The patients were all in hospital because of severe CHF and all were complaining of dyspnoea at rest (NYHA functional class IV). A radiographic heart size of more than 600 ml per square meter of body surface area in men (normal,
Muscle energy metabolism in severe chronic congestive heart failure — effect of treatment with enalapril M. BROQVIST*, U. DAHLSTROM*, E. KARLSSON* AND J. LARSSONI
From the Departments of * Cardiology and f Surgery, University of Health Sciences, Linkoping, Sweden KEY WORDS: Chronic heart failure, energy metabolism, enalapril, healthy individuals, muscle. Bv using biopsies, skeletal muscle metabolism was investigated in 22 patients with severe chronic heart failure. All the patients were in New York Heart Association functional class IV and constituted a subgroup of the previously published CONSENSUS trial. After this initial investigation ofmuscle metabolism in patients with chronic heartfailure, the influence of the angiotensin converting enzyme inhibitor, enalapril, on skeletal muscle metabolism was studied by randomizing the patients in a doubleblind manner to receive either placebo (n = 11) or enalapril (n=ll) in addition to conventional treatment. At the time of inclusion, the muscle content of energy-rich compounds, i.e. glycogen and the high energy phosphates, adenosine triphosphate (A TP) and phosphocrea tine, was reduced as compared with healthy subjects and muscle lactate content tended to be higher than normal. Following study treatment, no significant changes occurred, neither within nor between the two subgroups. Thus, patients with severe chronic congestive heart failure display metabolic derangement in muscle, which, in this study, was not corrected by treatment with enalapril. Introduction Exertional fatigue is frequently present in patients with congestive heart failure (CHF) but the correlations between cardiac function and exercise tolerance are weak'11. These findings have focused interest on the role of peripheral factors which limit exercise. Previous studies have revealed abnormal skeletal muscle metabolism during exercise in patients with CHF which might be due to inadequate blood flow1'-21. Angiotensin converting enzyme (ACE) inhibitors have vasodilating properties and have been shown to increase exercise tolerance in patients with heart failure131. The present investigation was conducted to examine skeletal muscle metabolism at rest in patients with severe chronic heart failure who have symptoms at rest (New York Heart Association functional class IV) and compare it to the situation in healthy individuals. We were also interested in investigating whether the addition of an ACE inhibitor (enalapril) to the conventional treatment with digitalis and diuretics might alter the skeletal muscle metabolism. Materials and methods PATIENTS
This study was performed in 22 patients participating in the CONSENSUS trial, which was a randomized, doubleblind, placebo-controlled, parallel-group trial studying the effects of enalapril on mortality in patients with severe congestive heart failure (CHF) New York Heart Association (NYHA) functional class IV14'. Because of a considerable reduction in mortality in the patients treated Submitted for publication on 15 July 1991, and in revised form 3 February 1992. Correspondence- Macs Broqvist, MD, Department of Cardiology, University Hospital, S-581 85 Linkoping, Sweden. 0195-66SX/92/091217 + 08 $08.00/0
with enalapril the CONSENSUS trial was discontinued ahead of schedule as recommended by the Ethical Review Committee141. The diagnosis of CHF was based on clinical criteria: a history of heart disease with symptoms of dyspnoea or fatigue or both, together with signs of fluid retention (pulmonary venous congestion, distended neck veins, hepatomegaly or peripheral oedema) and no evidence of primary pulmonary disease. The patients were all in hospital because of severe CHF and all were complaining of dyspnoea at rest (NYHA functional class IV). A radiographic heart size of more than 600 ml per square meter of body surface area in men (normal,
