title: Cinaciguat (BAY 58-2667) improves cardiopulmonary hemodynamics in patients with acute decompensated heart failure.
abstract: BACKGROUND
  Cinaciguat (BAY 58-2667) is the first of a new class of soluble guanylate cyclase activators in clinical development for acute decompensated heart failure. We aimed to assess the hemodynamic effects, safety, and tolerability of intravenous cinaciguat in patients with acute decompensated heart failure (pulmonary capillary wedge pressure > or =18 mm Hg).
  
  
  RESULTS
  After initial dose finding (part A; n=27), cinaciguat was evaluated in the nonrandomized, uncontrolled proof-of-concept part of the study (part B; n=33) using a starting dose of 100 microg/h, which could be titrated depending on hemodynamic response. Patients were categorized as responders if their pulmonary capillary wedge pressure decreased by > or =4 mm Hg compared with baseline. Final doses of cinaciguat after 6 hours of infusion in part B were 50 microg/h (n=2), 200 microg/h (n=12), and 400 microg/h (n=16). Compared with baseline, a 6-hour infusion of cinaciguat led to significant reductions in pulmonary capillary wedge pressure (-7.9 mm Hg), mean right atrial pressure (-2.9 mm Hg), mean pulmonary artery pressure (-6.5 mm Hg), pulmonary vascular resistance (-43.4 dynes . s . cm(-5)), and systemic vascular resistance (-597 dynes . s . cm(-5)), while increasing heart rate by 4.4 bpm and cardiac output by 1.68 L/min. The responder rate was 53% after 2 hours, 83% after 4 hours, and 90% after 6 hours. Cinaciguat was well tolerated, with 13 of 60 patients reporting 14 drug-related treatment-emergent adverse events of mild to moderate intensity, most commonly hypotension.
  
  
  CONCLUSIONS
  Cinaciguat has potent preload- and afterload-reducing effects, increasing cardiac output. Further investigation of cinaciguat for acute decompensated heart failure is warranted.
authors.affiliation: HELIOS Clinic Erfurt, Germany. harald.lapp@helios-kliniken.de
authors.forename: Harald
authors.initials: H
authors.lastname: Lapp
authors.forename: Veselin
authors.initials: V
authors.lastname: Mitrovic
authors.forename: Norbert
authors.initials: N
authors.lastname: Franz
authors.forename: Hubertus
authors.initials: H
authors.lastname: Heuer
authors.forename: Michael
authors.initials: M
authors.lastname: Buerke
authors.forename: Judith
authors.initials: J
authors.lastname: Wolfertz
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Mueck
authors.forename: Sigrun
authors.initials: S
authors.lastname: Unger
authors.forename: Georg
authors.initials: G
authors.lastname: Wensing
authors.forename: Reiner
authors.initials: R
authors.lastname: Frey
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001565:Benzoates / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006162:Guanylate Cyclase / Q000187:drug effects*; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects*; D000071756:Soluble Guanylyl Cyclase; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001565:Benzoates; D018160:Receptors, Cytoplasmic and Nuclear; D014665:Vasodilator Agents; C480588:BAY 58-2667; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase