Deloading of the left ventricle by ventricular assist device normalizes increased expression of endothelin ETA receptors but not endothelin-converting enzyme-1 in patients with end-stage heart failure

Background-Ventricular assist devices (VAD) are implanted in patients with end-stage heart failure for bridging the time until heart transplantation, resulting in hemodynamic unloading of the failing heart, improved cardiac c ontractile and mitochondrial function, and reversal of cardiac hypertrophy, It is unknown whether VAD unloading may affect the cardiac endothelin (ET) system, which has been proposed as one of the putative pathomechanisms of heart failure. Methods and Results-With the use of standard-calibrated, competitive revers e-transcription-polymerase chain reaction mRNA expression of components of the ET system was analyzed in left ventricular myocardium from nonfailing d onor hearts, from failing hearts without and with ACE inhibitor therapy, an d from patients with end-stage heart failure at the time of VAD implantatio n and 103+/-15 days after VAD implantation during removal with subsequent h eart transplantation. ET receptor A (ETA) was markedly upregulated in faili ng human myocardium. This increased ETA expression was not affected by ACE inhibitor treatment but was normalized by VAD unloading, ETA expression bef ore of after VAD implantation did not correlate with duration of VAD implan tation or suppression of Pro-ANP mRNA, ETB mRNA expression was unaffected b y heart failure or VAD. In contrast, increased ET-converting enzyme-1 mRNA and ET-I peptide levels in failing myocardium were partially normalized by ACE inhibition but not by VAD unloading, Conclusions-We conclude that VAD implantation normalizes ETA expression in failing human left ventricular myocardium, probably as the result of the be neficial effects of VAD unloading.