Open AccessBisoprolol therapy does not reduce right ventricular sympathetic activity in pulmonary arterial hypertension patients
Author(s) -
Rijnierse Mischa T.,
Groeneveldt Joanne A.,
Campen Jasmijn S.J.A.,
Boer Karin,
Bruggen Cathelijne E.E.,
Harms Hendrik J.,
Raijmakers Pieter G.,
Lammertsma Adriaan A.,
Knaapen Paul,
Bogaard Harm Jan,
Westerhof Berend E.,
Noordegraaf Anton Vonk,
Allaart Cornelis P.,
Man Frances S.
Publication year - 2020
Publication title -
pulmonary circulation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.791
H-Index - 40
ISSN - 2045-8940
DOI - 10.1177/2045894019873548
Subject(s) - medicine , bisoprolol , cardiology , ejection fraction , heart failure , anesthesia
Right ventricular (RV) function and autonomic dysfunction are important determinants of morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Although successful in animal studies, effects of beta‐blocker therapy on RV function in clinical trials were disappointing. To understand this discrepancy, we studied whether beta‐blocker therapy changes RV sympathetic activity. Idiopathic PAH (IPAH) patients received beta‐blocker therapy (uptitrated to a maximal tolerated dose) and underwent cardiac magnetic resonance imaging, right heart catheterization, and a [ 11 C]‐hydroxyephedrine positron emission tomography ([ 11 C]HED PET) scan at baseline to determine, respectively, RV ejection fraction (RVEF), RV pressures, and sympathetic activity. [ 11 C]HED, a norepinephrine analogue, allows determination of sympathetic innervation of the RV. [ 11 C]HED retention index reflects norepinephrine transporter activity. As a consequence of excessive catecholamine levels in the synaptic cleft, this transporter may be downregulated. Therefore, low [ 11 C]HED retention index indicates high sympathetic activity. 13 IPAH patients underwent [ 11 C]HED PET scans at baseline and after bisoprolol treatment. Although heart rate was reduced, systemic modulation of autonomic activity by bisoprolol did not affect local RV sympathetic nerve activity, RV function, or RV wall tension. In PAH patients, RV [ 11 C]HED retention index was lower compared to LV tracer uptake (p<0.01) and was related to systolic wall tension (R 2 = 0.4731, p<0.01) and RV function (R 2 = 0.44, p = 0.01). In RV failure, the tolerated dosage of bisoprolol did not result in an improvement of RV function nor in a reduction in RV sympathetic activity.