SPECIFIC CHANGES IN SKELETAL-MUSCLE MYOSIN HEAVY-CHAIN COMPOSITION INCARDIAC-FAILURE - DIFFERENCES COMPARED WITH DISUSE ATROPHY AS ASSESSED ON MICROBIOPSIES BY HIGH-RESOLUTION ELECTROPHORESIS

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 com paring patients with different degrees of CHF with patients with sever e muscle atrophy due to disuse. Design-Case-control study involving 50 -150 mu g needle biopsies of the gastrocnemius muscle. By an electroph oretic micromethod, the three isoforms of myosin heavy chains (MHC) we re separated. Patients-Five patients restricted to bed for more than o ne year because of stroke with disuse atrophy and normal ventricular f unction, and 19 with CHF were studied. There were seven age matched co ntrols. Main outcome measures-The percentage of MHC1 (slow isoform), M HC2a (fast oxidative), and MHC2b (fast glycolytic) was determined by d ensitometric scan and correlated with indices of severity of cardiac f ailure. 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/gast rocnemius 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 7.2 5 (7.92), P < 0.001]. There was a similar trend for MHC2a [24.83 (15.0 1) 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 MHC 2b (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 myo pathy appears to be specific and not related to detraining. The magnit ude of MCH redistribution correlates with the severity of the disease. The electrophoretic micromethod used is very sensitive and reproducib le. Biopsies are so well tolerated that can be repeated frequently, al lowing thorough follow up.