title: Change of right heart size and function by long-term therapy with riociguat in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.
abstract: BACKGROUND
  Riociguat is a soluble guanylate cyclase stimulator approved for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). The objective of this study was to evaluate the change of right heart size and function assessed by echocardiography during long-term treatment with riociguat.
  
  
  METHODS
  We assessed patients who started riociguat treatment (1.0-2.5mg tid) within the trials PATENT, PATENTplus, EAS and CHEST and continued for 3-12 months. Echocardiography, 6-minute walking distance (6MWD) and further clinical parameters were analyzed at baseline, after 3, 6 and 12 months. Right heart catheterization was performed at baseline and after 3 months. For missing data we performed the last and baseline observation carried forward (LOCF, BOCF) method as sensitivity analyses.
  
  
  RESULTS
  Thirty-nine patients (21 PAH, 18 CTEPH, mean pulmonary arterial pressure 43 ± 2 mmHg, PVR 600 ± 43 dyn ∗ s ∗ cm(-5), 56.4% treatment-naïve) were included. Mean right ventricular (RV) area significantly decreased after 3 (-2.1 ± 3.9 cm(2), equals -7.4 ± 15.3%, p = 0.002), 6 (-4.2 ± 3.2 cm(2), equals -16.1 ± 11.5%, p < 0.001) and 12 months (-5.9 ± 4.6 cm(2), equals -22.1 ± 14.2%, p < 0.001) compared to baseline. Right atrial area significantly decreased after 12 months (-3.5 ± 4.1cm(2), equals -16.8 ± 19.2%, p < 0.001) and TAPSE significantly improved after 6 (+ 2 ± 4.7, equals 12 ± 25.8%, p = 0.025) and 12 months (+ 3.6 ± 5.4, equals 21.0 ± 29.6%, p = 0.002). Furthermore, RV wall thickness and 6MWD significantly improved after 3, 6 and 12 months (p < 0.05). Invasive hemodynamics significantly improved after 3 months. Both LOCF and BOCF showed similar significance and lower effect sizes.
  
  
  CONCLUSIONS
  Long-term treatment with riociguat significantly reduced right heart size and improved RV function in PAH and CTEPH. Further prospective studies are needed to confirm these results.
authors.affiliation: Pulmonary Hypertension Center, Thoraxclinic at the University of Heidelberg, Germany; Internal Medicine Section-Department of Translational Medical Sciences, "Federico II" University School of Medicine, Naples, Italy.
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Marra
authors.affiliation: Pulmonary Hypertension Center, Thoraxclinic at the University of Heidelberg, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Egenlauf
authors.affiliation: Pulmonary Hypertension Center, Thoraxclinic at the University of Heidelberg, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Ehlken
authors.affiliation: Institute of Human Genetics, University Hospital Heidelberg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Fischer
authors.affiliation: Pulmonary Hypertension Center, Thoraxclinic at the University of Heidelberg, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Eichstaedt
authors.affiliation: Pulmonary Hypertension Center, Thoraxclinic at the University of Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Nagel
authors.affiliation: Cardiology Division, "Cava de' Tirreni and Amalfi Coast" Hospital, Heart Dept., University of Salerno - Italy and Cardiac Surgery Dept., IRCCS Policlinico San Donato, Milan, Italy.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bossone
authors.affiliation: Internal Medicine Section-Department of Translational Medical Sciences, "Federico II" University School of Medicine, Naples, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cittadini
authors.affiliation: Medical Clinic I, University Hospital of TU Dresden, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Halank
authors.affiliation: Department of Pneumology, University of Gießen Lung Center, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Gall
authors.affiliation: Department of Respiratory Medicine, Hannover Medical School, Germany.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Olsson
authors.affiliation: Internal Medicine II, University Medical Center Würzburg, Germany.
authors.forename: Tobias J
authors.initials: TJ
authors.lastname: Lange
authors.affiliation: Pulmonary Hypertension Center, Thoraxclinic at the University of Heidelberg, Germany. Electronic address: ekkehard.gruenig@med.uni-heidelberg.de.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Grünig
mesh_terms: D000328:Adult; D000368:Aged; D016280:Atrial Function, Right / Q000187:drug effects*; D002908:Chronic Disease; D004452:Echocardiography; D005080:Exercise Test; D005260:Female; D006162:Guanylate Cyclase / Q000378:metabolism*; D006325:Heart Atria; D006352:Heart Ventricles / Q000033:anatomy & histology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011655:Pulmonary Embolism / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D016896:Treatment Outcome; D016278:Ventricular Function, Right / Q000187:drug effects*; D016138:Walking / Q000502:physiology
chemical_list: D011720:Pyrazoles; D011743:Pyrimidines; D006162:Guanylate Cyclase; C542595:riociguat
keywords: Chronic thromboembolic pulmonary hypertension; Pulmonary arterial hypertension; Right atrium; Right ventricle; Riociguat