Skeletal muscle myosin heavy chains in heart failureCorrelation between magnitude of the isozyme shift, exercise capacity, and gas exchange measurements

Byline: Giorgio Vescovo, Francesco Serafini, Luciano Dalla Libera, Cristiana Leprotti, Luigi Facchin, Pierluigi Tenderini, Giovanni Battista Ambrosio Abstract: 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 MHC1 (slow aerobic isoform) and NYHA class (r.sup.2 = 0.62, p < 0.0001), peak VO.sub.2 (r.sup.2 =0.5, p < 0.0004), ventilatory threshold (VT) (r.sup.2 =0.33, p = 0.008) and O.sub.2 pulse (peak VO2/HR) (r.sup.2 = 0.40, p = 0.003). There was a negative correlation between both MHC2a (fast oxidative) and MHC2b (fast glycolytic) with peak VO2 (r.sup.2 = 0.38, p = 0.004 and r.sup.2 = 0.37, p = 0.004, respectively), VT (r.sup.2 = 0.2, p = 0.046 and r.sup.2 = 0.34, p = 0.007, respectively), and O.sub.2 pulse (peak VO.sub.2/HR) (r.sup.2 = 0.39, p = 0.003 and r.sup.2 = 0.23, p = 0.03). NYHA class was also correlated positively with MHC2a and MHC2b (r.sup.2 = 0.46, p = 0.001 and r.sup.2 = 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 VO.sub.2, VT, O.sub.2 pulse) seem to suggest that changes in skeletal muscle composition may play a determining role in exercise tolerance in patients with CHF. (Am Heart J 1998;135:130-7.) Author Affiliation: Venice and Padua, Italy Article History: Received 19 March 1997; Accepted 24 May 1997 Article Note: (footnote) [star] From the aFirst Department of Internal Medicine, Venice City Hospital, the bCNR Unit for Muscle Biology and Pathophysiology, University of Padua, and the cDepartment of Cardiology, Venice City Hospital., [star][star] Reprint requests: Giorgio Vescovo, MD, PhD, Internal Medicine I, Ospedale Civile di Venezia, SS Giovanni e Paolo, 30100 Venice, Italy., a 4/1/83774