However, application of the endothelin system blockade yielded controversial results [21,22,30–32], and the effects in heart failure patients, admittedly receiving nonselective endothelin receptor antagonist (bosentan) or presumably selective ETA antagonist (darusentan) were disappointing: early fluid retention actually leading to worsening of heart failure was a common finding [33–35]. The gene discussed is EDNRA; the disease is heart failure.