Why Levosimendan Improves the Clinical Condition of Patients With Advanced Heart Failure: A Holistic Approach.

Apostolo A; Vignati C; Della Rocca M; De Martino F; Berna G; Campodonico
J; Contini M; Muratori M; Palermo P; Mapelli M; Alimento M; Pezzuto B;
Agostoni P

Journal of Cardiac Failure. 28(3):509-514, 2022 03.

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

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.