title: Right ventricular diastolic dysfunction and the acute effects of sildenafil in pulmonary hypertension patients.
abstract: OBJECTIVE
  This study investigated whether right ventricular (RV) diastolic function is impaired in pulmonary hypertension (PH) patients, and whether it is related to RV mass and afterload. In addition, the effects of an acute reduction of RV afterload by the oral intake of sildenafil were studied. Finally, we assessed whether diastolic function is related to cardiac parameters of disease severity.
  
  
  RESULTS
  Twenty-five PH patients and 11 control subjects were studied. Right-heart catheterization and N-terminal pro-brain natriuretic peptide (NT-proBNP) sampling were performed in patients. MRI measured RV ejection fraction, mass, and diastolic function. Isovolumic relaxation time (IVRT), normalized early peak filling rate (E), atrium-induced peak filling rate (A), and E/A ratio described diastolic function. Compared to control subjects, patients had prolonged mean (+/- SD) IVRT (133.5 +/- 53.2 vs 29.3 +/- 20.8 ms, respectively; p < 0.001), decreased E (3.0 +/- 1.6 vs 6.4 +/- 2.5 s(-1), respectively; p < 0.001) and E/A ratio (1.1 +/- 0.7 vs 5.3 +/- 4.9, respectively; p < 0.001), and increased A (3.0 +/- 1.4 vs 1.5 +/- 0.9 s(-1), respectively; p = 0.001). IVRT was related to RV mass (r(25) = 0.56; p = 0.005) and pulmonary vascular resistance (r(25) = 0.74; p < 0.0001). Sildenafil therapy reduced RV afterload and improved RV diastolic and systolic function. IVRT was correlated with NT-proBNP level (r = 0.70; p < 0.001), and was inversely related to cardiac index (r = -0.70; p < 0.001) and RV ejection fraction (r = -0.69; p < 0.001).
  
  
  CONCLUSIONS
  In PH patients, RV diastolic dysfunction is related to RV mass and afterload. RV diastolic function improves by reducing afterload. The correlations between diastolic function and prognostic parameters showed that diastolic function is most impaired in patients with severe disease.
authors.affiliation: VU University Medical Center, De Boelelaan 1117 PO Box 7057, 1007 MB Amsterdam, the Netherlands.
authors.forename: C Tji-Joong
authors.initials: CT
authors.lastname: Gan
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Holverda
authors.forename: J Tim
authors.initials: JT
authors.lastname: Marcus
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Paulus
authors.forename: Koen M
authors.initials: KM
authors.lastname: Marques
authors.forename: Jean G F
authors.initials: JG
authors.lastname: Bronzwaer
authors.forename: Jos W
authors.initials: JW
authors.lastname: Twisk
authors.forename: Anco
authors.initials: A
authors.lastname: Boonstra
authors.forename: Pieter E
authors.initials: PE
authors.lastname: Postmus
authors.forename: Anton
authors.initials: A
authors.lastname: Vonk-Noordegraaf
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001775:Blood Circulation / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D000077300:Bosentan; D011464:Epoprostenol / Q000627:therapeutic use; D005260:Female; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000627:therapeutic use; D010879:Piperazines / Q000627:therapeutic use*; D011687:Purines / Q000627:therapeutic use; D012720:Severity of Illness Index; D000068677:Sildenafil Citrate; D013318:Stroke Volume / Q000502:physiology; D013449:Sulfonamides / Q000627:therapeutic use; D013450:Sulfones / Q000627:therapeutic use*; D014655:Vascular Resistance / Q000502:physiology; D014665:Vasodilator Agents / Q000627:therapeutic use*; D018497:Ventricular Dysfunction, Right / Q000503:physiopathology*
chemical_list: D000959:Antihypertensive Agents; D010879:Piperazines; D011687:Purines; D013449:Sulfonamides; D013450:Sulfones; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000068677:Sildenafil Citrate; D011464:Epoprostenol; D000077300:Bosentan