Combined beta1-inhibition with beta2-stimulation with clenbuterol has been proposed as a ttt modality to achieve sustained reversal of severe HF in selected pts requiring LV assist devices(1). The rationale for this approach was based on experimental studies demonstrating that clenbuterol ttt, alone or in combination with mechanical unloading, improved LV function at the whole-heart and cellular levels by affecting cell morphology, excitation-contraction coupling, and myofilament sensitivity to calcium(2).

After optimization of medical therapy and achieving a constant LV size for at least 2 weeks, clenbuterol was administered at an initial dose of 40 ug twice daily, then at a dose of 40 ug 3 times daily, and finally at a dose of 700 ug 3 times daily. The dose was adjusted to maintain resting heart rate at a level below 100 beats/min. Prior to clenbuterol initiation, carvedilol was replaced by the selective beta1-blocker bisoprolol.

It should be taken into consideration, however, that in a recent small, randomized controlled study, clenbuterol use in pts with chronic HF was associated with a significant increase in both lean mass and lean/fat ratio as well as in muscle strength, and a decrease in exercise duration(3). Thus, the effectiveness of clenbuterol in HF pts should be further evaluated in larger prospective trials.

References:

1. Birks EJ, Tansley PD, Hardy J, et al. Left ventricular assist device and drug therapy for the reversal of heart failure. N Engl J Med 2006;355:1873– 84.
2. Soppa GK, Lee J, Stagg MA, et al. Role and possible mechanisms of clenbuterol in enhancing reverse remodelling during mechanical unloading in murine heart failure. Cardiovasc Res 2008;77:695–706.
3. Kamalakkannan G, Petrilli CM, George I, et al. Clenbuterol increases lean muscle mass but not endurance in patients with chronic heart failure. J Heart Lung Transplant 2008;27:457– 61.