title: Bisoprolol in idiopathic pulmonary arterial hypertension: an explorative study.
abstract: While beta-blockers are considered contraindicated in pulmonary arterial hypertension (PAH), the prognostic significance of sympathetic nervous system over-activity suggests a potential benefit of beta-blocker therapy. The aim of this randomised, placebo-controlled, crossover, single centre study was to determine the effects of bisoprolol on right ventricular ejection fraction (RVEF) in idiopathic PAH (iPAH) patients. Additional efficacy and safety parameters were explored.Patients with optimally treated, stable iPAH (New York Heart Association functional class II/III) were randomised to placebo or bisoprolol. Imaging and functional measurements were performed at baseline, crossover and end of study.18 iPAH patients were included, because inclusion faltered before enrolment of the targeted 25 patients. 17 patients completed 6 months of bisoprolol, 15 tolerated bisoprolol, one patient required intravenous diuretics. Bisoprolol was associated with a lower heart rate (17 beats per minute, p=0.0001) but RVEF remained unchanged. A drop in cardiac index (0.5 L·min(-1)·m(-2), p=0.015) was observed, along with a trend towards a decreased 6-min walking distance (6MWD).Although careful up-titration of bisoprolol was tolerated by most patients and resulted in a decreased heart rate, no benefit of bisoprolol in iPAH was demonstrated. Decreases in cardiac index and 6MWD suggest a deteriorated cardiac function. The results do not favour the use of bisoprolol in iPAH patients.
authors.affiliation: Dept of pulmonary medicine, Institute for cardiovascular research, VU University medical center, Amsterdam, The Netherlands Both authors contributed equally.
authors.forename: Jasmijn S J A
authors.identifier: 0000-0003-0703-4601
authors.initials: JS
authors.lastname: van Campen
authors.affiliation: Dept of cardiology, Institute for cardiovascular research, VU University medical center, Amsterdam, The Netherlands Both authors contributed equally.
authors.forename: Karin
authors.initials: K
authors.lastname: de Boer
authors.affiliation: Dept of pulmonary medicine, Institute for cardiovascular research, VU University medical center, Amsterdam, The Netherlands Dept of cardiology, Institute for cardiovascular research, VU University medical center, Amsterdam, The Netherlands.
authors.forename: Mariëlle C
authors.initials: MC
authors.lastname: van de Veerdonk
authors.affiliation: Dept of pulmonary medicine, Institute for cardiovascular research, VU University medical center, Amsterdam, The Netherlands.
authors.forename: Cathelijne E E
authors.initials: CE
authors.lastname: van der Bruggen
authors.affiliation: Dept of cardiology, Institute for cardiovascular research, VU University medical center, Amsterdam, The Netherlands.
authors.forename: Cor P
authors.initials: CP
authors.lastname: Allaart
authors.affiliation: Dept of nuclear medicine and PET-research, VU University medical center, Amsterdam, The Netherlands.
authors.forename: Pieter G
authors.initials: PG
authors.lastname: Raijmakers
authors.affiliation: Dept of epidemiology, VU University medical center, Amsterdam, The Netherlands.
authors.forename: Martijn W
authors.initials: MW
authors.lastname: Heymans
authors.affiliation: Dept of physics and medical technology, VU University medical center, Amsterdam, The Netherlands.
authors.forename: J Tim
authors.initials: JT
authors.lastname: Marcus
authors.affiliation: Dept of pulmonary medicine, Institute for cardiovascular research, VU University medical center, Amsterdam, The Netherlands Dept of nuclear medicine and PET-research, VU University medical center, Amsterdam, The Netherlands.
authors.forename: Hendrik J
authors.initials: HJ
authors.lastname: Harms
authors.affiliation: Dept of cardiology, Institute for cardiovascular research, VU University medical center, Amsterdam, The Netherlands.
authors.forename: M Louis
authors.initials: ML
authors.lastname: Handoko
authors.affiliation: Dept of pulmonary medicine, Institute for cardiovascular research, VU University medical center, Amsterdam, The Netherlands Dept of physiology, Institute for cardiovascular research, VU University medical center, Amsterdam, The Netherlands.
authors.forename: Frances S
authors.initials: FS
authors.lastname: de Man
authors.affiliation: Dept of pulmonary medicine, Institute for cardiovascular research, VU University medical center, Amsterdam, The Netherlands.
authors.forename: Anton
authors.initials: A
authors.lastname: Vonk Noordegraaf
authors.affiliation: Dept of pulmonary medicine, Institute for cardiovascular research, VU University medical center, Amsterdam, The Netherlands Dept of physiology, Institute for cardiovascular research, VU University medical center, Amsterdam, The Netherlands hj.bogaard@vumc.nl.
authors.forename: Harm-Jan
authors.initials: HJ
authors.lastname: Bogaard
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D017298:Bisoprolol / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015444:Exercise; D065627:Familial Primary Pulmonary Hypertension / Q000188:drug therapy*; D005260:Female; D006333:Heart Failure / Q000150:complications; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D016277:Ventricular Function, Left; D016278:Ventricular Function, Right; D016138:Walking
chemical_list: D000959:Antihypertensive Agents; D017298:Bisoprolol