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Background: In congestive heart failure, fatigue-resistant, oxidative, slow type I fibers are decreased in leg skeletal muscle, contributing to exercise capacity (EC) limitation. The mechanisms by which ACE inhibitors and AII antagonists improve EC is still unclear. We tested the hypothesis that improvement in EC is related to changes in skeletal muscle composition toward type I fibers., Methods and Results: Eight patients with congestive heart failure, NYHA classes I through IV, were treated for 6 months with enalapril (E) 20 mg/d, and another 8 with losartan (L) 50 mg/d. EC was assessed with maximal cardiopulmonary exercise testing at baseline and after treatment. Myosin heavy chain (MHC) composition of the gastrocnemius was studied after electrophoretic separation of slow MHC1, fast oxidative MHC2a, and fast glycolytic MHC2b isoforms from needle microbiopsies obtained at baseline and after 6 months. EC improved in both groups. Peak V(O2) increased from 21.0+/-4.7 to 27.6+/-4.3 mL . kg-1 . min -1 (P=0.011) in the L group and from 17.5+/-5.0 to 25.0+/-5.5 mL . kg-1 . min -1 (P=0.014) in the E group. Similarly, ventilatory threshold changed from 15.0+/-4.0 to 19.9+/-4.9 mL (P=0. 049) with L and from 12.0+/-1.9 to 15.4+/-3.5 mL (P=0.039) with E. MCH1 increased from 61.2+/-11.2% to 75.4+/-7.6% with L (P=0.012) and from 60.6+/-13.1% to 80.1+/-10.9% (P=0.006) with E. Similarly, MHC2a decreased from 21.20+/-9.5% to 12.9+/-4.4% (P=0.05) with L and from 19.9+/-7.8% to 11.8+/-7.9% (P=0.06) with E. MHC2b changed from 17. 5+/-6.5% to 11.7+/-5.2% (P=0.07) with L and from 19.5+/-6.4% to 8. 1+/-4.6% (P=0.0015) with E. There was a significant correlation between net changes in MHC1 and absolute changes in peak V(O2) (r2=0.29, P=0.029) and a trend to significance for MHC2a and 2b., Conclusions: Six months' treatment with L and with E produces an improvement in EC of similar magnitude. These changes are accompanied by a reshift of MHCs of leg skeletal muscle toward the slow, more fatigue-resistant isoforms. Magnitude of MHC1 changes correlates with the net peak V(O2) gain, which suggests that improved EC may be caused by favorable biochemical changes occurring in the skeletal muscle.

Background: Patients with congestive heart failure (CHF) have a reduced exercise capacity because of the early appearance of fatigue and dyspnea. Qualitative changes in the skeletal muscle composition and metabolism can be responsible for the origin of symptoms, Methods: We correlated the myosin heavy chain (MHC) composition of the gastrocnemius in 20 patients with different degrees of CHF to NYHA class, diuretic consumption, echocardiographic parameters, and expiratory gases measured during cardiopulmonary exercise testing. MHC composition was determined electrophoretically in skeletal muscle needle microbiopsies and the percent distribution was calculated by densitometry. Maximal cardiopulmonary exercise testing was performed on a treadmill with a modified Naughton protocol. A capnograph was used., Results: There was no correlation between ejection fraction, left ventricular end systolic diameter, left ventricular end diastolic diameter, and MHC composition. We found a significant positive correlation between the percentage of MHC 1 (slow aerobic isoform) and NYHA class (r2 = 0.62, p < 0.0001), peak VO2 (r2 = 0.5, p < 0.0004), ventilatory threshold (VT) (r2 = 0.33, p = 0.008) and O2 pulse (peak VO2/HR) (r2 = 0.40, p = 0.003). There was a negative correlation between both MHC2a (fast oxidative) and MHC2b (fast glycolytic) with peak VO2 (r2 = 0.38, p = 0.004 and r2 = 0.37, p = 0.004, respectively), VT (r2 = 0.2, p = 0.046 and r2 = 0.34, p = 0.007, respectively), and O2 pulse (peak VO2/HR) (r2 = 0.39, p = 0.003 and r2 = 0.23, p = 0.03). NYHA class was also correlated positively with MHC2a and MHC2b (r2 = 0.46, p = 0.001 and r2 = 0.41, p < 0.006, respectively) and negatively with the same clinical and functional parameters., Conclusions: The correlation between the magnitude of the MHC shift from the slow aerobic to the fast glycolytic and fast oxidative with both functional and objective measurements of exercise capacity (peak VO2, VT, O2 pulse) seem to suggest that changes in skeletal muscle composition may play a determining role in exercise tolerance in patients with CHF.

Chronic heart failure (CHF) is accompanied by a reduced exercise capacity, and the symptoms can be at least in part explained by qualitative and quantitative changes in the skeletal muscle composition and metabolism. We have correlated the myosin heavy chain (MHC) composition of the gastrocnemius in 20 patients with different degrees of CHF to expiratory gases measured during maximal cardiopulmonary exercise testing, NYHA functional class and echocardiographic parameters. MHC composition was determined electrophoretically in skeletal muscle needle microbiopsies and the percent distribution calculated by laser densitometry. There was no correlation between ejection fraction, left ventricular end-diastolic and end-systolic diameters and MHC composition. The percentage of MHC 1 (slow aerobic isoform) was positively correlated with peak VO2 (r2 = 0.5, p = 0.0004), ventilatory threshold (VT, r2 = 0.33, p = 0.008), and O2 pulse (peak VO2/HR, r2 = 0.40, p = 0.003). There was a negative correlation between MHC 2a and 2b (fast isoforms) and peak VO2 (r2 = 0.38 and 0.37, p = 0.004, respectively), VT (r2 = 0.2, p = 0.05; r2 = 0.34, p = 0.007, respectively) and O2 pulse (r2 = 0.39, p = 0.003; r2 = 0.23, p = 0.03, respectively). NYHA functional class was also negatively correlated with the same parameters (r2 = 0.2, p = 0.01; r2 = 0.4, p = 0.001; r2 = 0.34, p = 0.006, respectively) as well as with MHC 1 (r2 = 0.62, p = 0.0001). A positive correlation was found between NYHA functional class and MHC 2a and 2b (r2 = 0.46, p = 0.001; r2 = 0.41, p = 0.002, respectively). The severity of heart failure is paralleled by a shift of the MHC pattern toward the fast MHC 2b. The correlation between the magnitude of the MHCs shift, from the slow aerobic to the fast type, with both clinical parameters (NYHA functional class) and functional measurements (peak VO2, VT, O2 pulse) of exercise capacity seem to suggest that changes in skeletal muscle composition may play a key role in exercise tolerance in patients with CHF.

Objective: In congestive heart failure (CHF) the skeletal muscle of the lower limbs develops a myopathy with atrophy and shift from the slow type to the fast type fibres. The aim was to test the hypothesis that this myopathy is specific and not simply related to detraining, by comparing patients with different degrees of CHF with patients with severe muscle atrophy due to disuse., Design: Case-control study involving 50-150 micrograms needle biopsies of the gastrocnemius muscle. By an electrophoretic micromethod, the three isoforms of myosin heavy chains (MHC) were separated., Patients: Five patients restricted to bed for more than one year because of stroke with disuse atrophy and normal ventricular function, and 19 with CHF were studied. There were seven age matched controls., Main Outcome Measures: The percentage of MHC1 (slow isoform), MHC2a (fast oxidative), and MHC2b (fast glycolytic) was determined by densitometric scan and correlated with indices of severity of cardiac failure., Results: Ejection fraction was 42.5 (SD 15.2)% in CHF, 59.5 (1.0)% in disuse atrophy and 60.3 (1.4)% in controls (P < 0.001 v both). The degree of muscle atrophy as calculated by the body mass index/gastrocnemius cross sectional area, showed a profound degree of atrophy in patients with muscle disuse [0.94 (0.39)]. This was worse than in the controls [4.27 (0.16), P < 0.0005] and the CHF patients [2.60 (1.10), P < 0.005]. Atrophy in CHF patients was also greater than in controls (P < 0.005). MHC1 was lower in CHF than in disuse atrophy [51.83 (15.04) v 84.5 (17.04), P < 0.01] while MHC2b was higher [23.5 (7.4) v 7.25 (7.92), P < 0.001]. There was a similar trend for MHC2a [24.83 (15.01) v 8.25 (9.12), P < 0.05]. Within the CHF group there was a positive correlation between NYHA class and MHC2a (r = 0.47, P < 0.05) and MHC2b (r = 0.55, P < 0.01) and a negative correlation between NYHA class and MHC1 (r = -0.74, P < 0.001). Similarly, significant correlations were found for ejection fraction, diuretic consumption score, exercise test tolerance, and degree of muscle atrophy., Conclusions: The CHF myopathy appears to be specific and not related to detraining. The magnitude of MCH redistribution correlates with the severity of the disease. The electrophoretic micromethod used is very sensitive and reproducible. Biopsies are so well tolerated that can be repeated frequently, allowing thorough follow up.