[Show abstract][Hide abstract] ABSTRACT: Myostatin inhibits myoblast differentiation/proliferation and may play a role in heart failure (HF) and reverse remodelling after left ventricular assist device (LVAD) support. This study sought to characterize myostatin expression and activation in advanced HF before and after LVAD support.
Left ventricular tissue pairs were collected at LVAD implantation (core) and at cardiac transplantation/LVAD explantation in patients with advanced ischaemic (ICM-ischaemic cardiomyopathy) and non-ischaemic (DCM-dilated cardiomyopathy) HF. Normal cardiac tissue (control) was obtained from hearts not placed for transplantation. Serum was collected independently from patients with stable DCM HF and from healthy controls. Full-length and cleaved propeptide myostatin levels were quantified by western blot analysis. Dilated cardiomyopathy propeptide levels at core were significantly higher than control and significantly increased after LVAD support. Ischaemic cardiomyopathy propeptide levels were higher than control, but did not change after LVAD support. No changes in full-length levels were seen. Serum myostatin levels were significantly higher in DCM HF patients than in healthy controls.
This is the first clinical evidence that myostatin activation is increased in HF. Myostatin may affect cardiac hypertrophy and may mediate regression of cellular hypertrophy after mechanical unloading.
European Journal of Heart Failure 03/2010; 12(5):444-53. · 5.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hemodynamic responses to exercise were assessed in patients with varying degrees of chronic heart failure (CHF) to determine the feasibility of using bioreactance during exercise testing in multicenter studies of CHF.
A total of 210 symptomatic CHF patients and 22 subjects without heart failure were subjected to symptom-limited exercise testing on a bicycle (105) or treadmill (127) while measuring gas exchange for VO(2), cardiac output (CO) noninvasively by a bioreactance technique, heart rate, and blood pressure. Peak CO (pCO) and VO(2) (pVO(2)) during exercise were lower in patients with higher New York Heart Association (NYHA) class, in females and in older patients. Multiple linear regression analysis showed that pCO (L/min)=19.6+4.M -2.1.NYHA+1.9.G -0.09.Age, where M=1 for treadmill and 0 for bicycle and G=1 for males and 0 for females. Similarly, pVO(2) (mL/kg/min)=24+2.1.M -2.9.NYHA+1.26.G -0.08.Age. VO(2) and CO were also highly correlated to each other: pCO (mL/kg/min)=0.059+0.007.pVO(2)+0.036.M -0.025.G. Similar correlations were determined for other parameters of exercise, including left ventricular power, and the ratio of peak/resting VO(2) (cardiovascular reserve), the ratio of peak/resting CO (cardiac reserve), and total peripheral vascular resistance.
Bioreactance-based noninvasive measurements of CO at rest and during exertion identified abnormalities of cardiovascular function consistent with those identified by pVO(2) and in prior studies using invasive CO measurements. This technique might therefore be useful for indexing disease severity, prognostication, and for tracking responses to treatment in clinical practice and in clinical trials.
Journal of cardiac failure 10/2009; 15(8):689-99. · 3.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Clenbuterol, a beta(2)-agonist with potent anabolic properties, has been shown to improve skeletal muscle function in healthy subjects, and in high doses, promotes cardiac recovery in patients with left ventricular assist devices. In a small, randomized controlled study, we investigated the effect of clenbuterol on skeletal muscle function, cardiac function, and exercise capacity in patients with chronic heart failure. Clenbuterol was well tolerated and led to a significant increase in both lean mass and the lean/fat ratio. Maximal strength increased significantly with both clenbuterol (27%) and placebo (14%); however, endurance and exercise duration decreased after clenbuterol. Prior data support combining exercise training with clenbuterol to maximize performance, and on-going studies will evaluate this approach.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 05/2008; 27(4):457-61. · 5.61 Impact Factor