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

Published:November 08, 2021DOI:https://doi.org/10.1016/j.cardfail.2021.10.009

      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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      References

        • Papp Z
        • Agostoni P
        • Alvarez J
        • Bettex D
        • Bouchez S
        • Brito D
        • et al.
        Levosimendan efficacy and safety: 20 years of SIMDAX in clinical use.
        Cardiac Fail Rev. 2020; 6: e19
        • Wasserman K
        • Zhang YY
        • Gitt A
        • Belardinelli R
        • Koike A
        • Lubarsky L
        • et al.
        Lung function and exercise gas exchange in chronic heart failure.
        Circulation. 1997; 96: 2221-2222
        • Agostoni P
        • Dumitrescu D
        How to perform and report a cardiopulmonary exercise test in patients with chronic heart failure.
        Int J Cardiol. 2019; 288: 107-113
        • Agostoni P
        • Bianchi M
        • Moraschi A
        • Palermo P
        • Cattadori G
        • La Gioia R
        • Bussotti M
        • et al.
        Work-rate affects cardiopulmonary exercise test results in heart failure.
        Eur J Heart Fail. 2005; 7: 498-504
        • Guazzi M
        • Marenzi G
        • Assanelli E
        • Perego GB
        • Cattadori G
        • Doria E
        • et al.
        Evaluation of the dead space/tidal volume ratio in patients with chronic congestive heart failure.
        J Cardiac Fail. 1995; 1: 401-408
        • Agostoni P
        • Cattadori G
        • Bianchi M
        • Wasserman K.
        Exercise-induced pulmonary edema in heart failure.
        Circulation. 2003; 108: 2666-2671
        • Chua TP
        • Clark AL
        • Amadi AA
        • Coats AJ.
        Relation between chemosensitivity and the ventilatory response to exercise in chronic heart failure.
        J Am Coll Cardiol. 1996; 27: 650-657
        • Cattadori G
        • Schmid JP
        • Brugger N
        • Gondoni E
        • Palermo P
        • Agostoni P.
        Hemodynamic effects of exercise training in heart failure.
        J Cardiac Fail. 2011; 17: 916-922