Abstract
Background
In advanced heart failure (HF), levosimendan increases peak oxygen uptake (VO2). We investigated whether peak VO2 increase is linked to cardiovascular, respiratory, or muscular performance changes.
Methods and Results
Twenty patients hospitalized for advanced HF underwent, before and shortly after levosimendan
infusion, 2 different cardiopulmonary exercise tests: (a) a personalized ramp protocol
with repeated arterial blood gas analysis and standard spirometry including alveolar–capillary
gas diffusion measurements at rest and at peak exercise, and (b) a step incremental
workload cardiopulmonary exercise testing with continuous near-infrared spectroscopy
analysis and cardiac output assessment by bioelectrical impedance analysis.Levosimendan
significantly decreased natriuretic peptides, improved peak VO2 (11.3 [interquartile range 10.1–12.8] to 12.6 [10.2–14.4] mL/kg/min, P < .01) and decreased minute ventilation to carbon dioxide production relationship slope
(47.7 ± 10.7 to 43.4 ± 8.1, P < .01). In parallel, spirometry showed only a minor increase in forced expiratory volume,
whereas the peak exercise dead space ventilation was unchanged. However, during exercise,
a smaller edema formation was observed after levosimendan infusion, as inferable from
the changes in diffusion components, that is, the membrane diffusion and capillary
volume. The end-tidal pressure of CO2 during the isocapnic buffering period increased after levosimendan (from 28 ± 3 mm
Hg to 31 ± 2 mm Hg, P < .01). During exercise, cardiac output increased in parallel with VO2. After levosimendan, the total and oxygenated tissue hemoglobin, but not deoxygenated
hemoglobin, increased in all exercise phases.
Conclusions
In advanced HF, levosimendan increases peak VO2, decreases the formation of exercise-induced lung edema, increases ventilation efficiency
owing to a decrease of reflex hyperventilation, and increases cardiac output and muscular
oxygen delivery and extraction.
Key Words
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Article info
Publication history
Published online: November 08, 2021
Accepted:
October 12,
2021
Received in revised form:
September 21,
2021
Received:
August 4,
2021
Identification
Copyright
© 2021 Elsevier Inc. All rights reserved.
