Abstract
Diastolic dysfunction (DD) in heart failure is associated with increased myocardial cytosolic calcium and calcium-efflux through the sodium–calcium exchanger depends on the sodium gradient. Beta-3-adrenoceptor (β3-AR) agonists lower cytosolic sodium and have reversed organ congestion. Accordingly, β3-AR agonists might improve diastolic function, which we aimed to assess. In a first-in-man, randomized, double-blinded trial, we assigned 70 patients with HF with reduced ejection fraction, New York Heart Association II-III, and left ventricular ejection fraction <40% to receive the β3-AR agonist mirabegron (300 mg/day) or placebo for 6 months, in addition to recommended heart failure therapy. We performed echocardiography and cardiac computed tomography and measured N-terminal probrain natriuretic peptide at baseline and follow-up. DD was graded per multiple renowned algorithms. Baseline and follow-up data were available in 57 patients (59 ± 11 years, 88% male, 49% ischemic heart disease). No clinically significant changes in diastolic measurements were found within or between the groups by echocardiography (E/e′ placebo: 13 ± 7 to 13 ± 5, P = 0.21 vs. mirabegron: 12 ± 6 to 13 ± 8, P = 0.74, between-group follow-up difference 0.2 [95% CI, −3 to 4], P = 0.89) or cardiac computed tomography (left atrial volume index: between-group follow-up difference 9 mL/m2 [95% CI, −3 to 19], P = 0.15). DD gradings did not change within or between the groups following 2 algorithms (P = 0.72, P = 0.75). N-terminal probrain natriuretic peptide remained unchanged in both the groups (P = 0.74, P = 0.64). In patients with HF with reduced ejection fraction, no changes were identified in diastolic measurements, gradings or biomarker after β3-AR stimulation compared with placebo. The findings add to the previous literature questioning the role of impaired Na+-Ca2+–mediated calcium export as a major culprit in DD.
Originalsprog | Engelsk |
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Tidsskrift | Journal of Cardiovascular Pharmacology |
Vol/bind | 83 |
Udgave nummer | 5 |
Sider (fra-til) | 466-473 |
Antal sider | 8 |
ISSN | 0160-2446 |
DOI | |
Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:Supported by The Heart Centre Research Foundation, Rigshospitalet; The A.P. M\u00F8ller and Chastine Mc-Kinney M\u00F8ller Foundation; and The Novo Nordic Foundation. The sponsors did not influence the study's design or the collection, analysis or interpretation of data, the writing of the manuscript, or the decision to submit the manuscript for publication.
Publisher Copyright:
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