Response to Letter Regarding Article, “Direct Myocardial Effects of Levosimendan in Humans With Left Ventricular Dysfunction: Alteration of Force-Frequency and Relaxation-Frequency Relationships”
We thank Guarracino et al for their comments about our study,1 in which we demonstrated that levosimendan exerts mild positive inotropic and lusitropic effects in humans with left ventricular dysfunction but does not alter the slope of the force-frequency or relaxation-frequency relationship. Guarracino et al have preliminary data suggesting that levosimendan also improves ventriculoarterial coupling in heart failure, and they raise the possibility that “arterial destiffening” may explain some of our results. However, unlike their study using intravenous drug administration, we infused levosimendan directly into the left main coronary artery, thereby avoiding changes in loading conditions that might confound the interpretation of myocardial contractility and relaxation. With this approach, we cannot comment on the effects of levosimendan on arterial elastance. However, prior studies2 have shown that intravenous administration of levosimendan causes systemic vasodilation, in part via opening of adenosine triphosphatase-sensitive K+ channels.
Givertz MM, Andreou C, Conrad CH, Colucci WS. Direct myocardial effects of levosimendan in humans with left ventricular dysfunction: alteration of force-frequency and relaxation-frequency relationships. Circulation. 2007; 115: 1218–1224.
Slawsky MT, Colucci WS, Gottlieb SS, Greenberg BH, Haeusslein E, Hare J, Hutchins S, Leier CV, LeJemtel TH, Loh E, Nicklas J, Ogilby D, Singh BN, Smith W. Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure. Study Investigators. Circulation. 2000; 102: 2222–2227.