Levosimedan improves hemodynamics functions without sympathetic activation in severe heart failure patients: Direct evidence from sympathetic neural recording

Despas, Fabien; Trouillet, Charlotte; Franchitto, Nicolas; Labrunée, M.; Galinier, Michel; Senard, Jean‐Michel; Pathak, Atul

doi:10.3109/17482940903434077

Cited by 12 publications

(8 citation statements)

References 26 publications

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“…The direct intraneural recording of MSNA after levosimendan administration in chronic heart failure patients showed a significant decrease in this activity. This occurs in parallel to the expected effect of levosimendan on cardiac performance with an increase in cardiac output and stroke volume and without associated bradycardia . The diminution of MSNA activity in this study suggests better benefice/risk ratio of levosimendan than other positive inotropes.…”

Section: Resultssupporting

confidence: 72%

“…This occurs in parallel to the expected effect of levosimendan on cardiac performance with an increase in cardiac output and stroke volume and without associated bradycardia. 58 The diminution of MSNA activity in this study suggests better benefice/risk ratio of levosimendan than other positive inotropes.…”

Section: Pharmacodynamics and Clinical Effects Of The Levosimendanmentioning

confidence: 57%

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Pharmacology of levosimendan: inotropic, vasodilatory and cardioprotective effects

et al. 2013

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SUMMARYWhat is known and objective: Positive inotropic agents are frequently used in acute decompensated heart failure (ADHF) due to left ventricular systolic dysfunction. These agents are known to improve cardiac performance and peripheral perfusion in the short-term treatment. However, several preclinical and clinical studies emphasized detrimental effects of these drugs on myocardial oxygen demand and on sympathetic tone entailing arrhythmogenesis. Levosimendan is an inotropic agent with an original mechanism of action. This review focuses on major data available for levosimendan. Methods: A literature search was conducted in the PubMed database by including studies published in English using combinations of the following key words, levosimendan, inotropic drugs and acute heart failure. Furthermore, bibliographies of selected references were also evaluated for relevant articles. The collection for this review was limited to the most recently available human and animal data. Results and discussion: Levosimendan's vasodilatory and cardioprotective effects are mediated by calcium sensitization of contractile proteins and opening of adenosine triphosphate (ATP)-dependent K+ channels in vascular smooth muscle cells and on mitochondrial ATP-sensitive potassium [mito.K(ATP)] channels. This inotropic agent has mild PDE inhibitory action. Unlike other inotropic agents, levosimendan improves cardiac performance without activating the sympathetic nervous system. Moreover, there are evidences that levosimendan has additional anti-inflammatory and anti-apoptotic properties that prevent cardiac toxicity and contributes to positive hemodynamic response of the drug. Four randomized trials evaluated the effects of levosimendan on mortality in patients with acute decompensated chronic heart failure; nevertheless, a clear benefit has not been demonstrated so far. Although levosimendan is indicated for the treatment of ADHF (class of recommendation IIa, level of evidence B), it is has not been approved in all countries.

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Section: Resultssupporting

confidence: 72%

Section: Pharmacodynamics and Clinical Effects Of The Levosimendanmentioning

confidence: 57%

Pharmacology of levosimendan: inotropic, vasodilatory and cardioprotective effects

et al. 2013

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“…We have previously validated relative change in SV by DPP in comparison with that by echocardiographic-Doppler during various respiratory maneuvers, confirming that DPP can provide valid estimates of relative changes in SV that occur over time [10]. In addition, DPP has been used to evaluate SV responses to drug intervention in patients with low SV due to decompensated HFrEF [39].…”

Section: Limitationsmentioning

confidence: 62%

Relationship of stroke volume to different patterns of Cheyne-Stokes respiration in heart failure

Inami

Kasai

Yumino

et al. 2019

Sleep

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Study Objectives: In patients with heart failure (HF) and reduced left ventricular ejection fraction (HFrEF), stroke volume (SV) falls during hyperpnea of Cheyne-Stokes respiration with central sleep apnea (CSR-CSA). We have identified two distinct patterns of hyperpnea: positive, in which end-expiratory lung volume (EELV) remains at or above functional residual capacity (FRC), and negative, in which EELV falls below FRC. The increase in expiratory intrathoracic pressure generated by the latter should have effects on the heart analogous to external chest compression. To test the hypotheses that in HFrEF patients, CSR-CSA with the negative pattern has an auto-resuscitation effect such that compared with the positive pattern, it is associated with a smaller fall in SV and a smaller increase in cardiac workload (product of heart rate and systolic blood pressure). Methods: In 15 consecutive HFrEF patients with CSR-CSA during polysomnography, hemodynamic data derived from digital photoplethysmography during positive and negative hyperpneas were compared. Results: Compared to the positive, negative hyperpneas were accompanied by reductions in the maximum and mean relative fall in SV of 30% (p = 0.002) and 10% (p = 0.031), respectively, and by reductions in the degree of increases in heart rate and rate pressure product during hyperpnea of 46% (p < 0.001) and 13% (p = 0.007), respectively. Conclusions: Our findings suggest the novel concept that the negative pattern of CSR-CSA may constitute a form of auto-resuscitation that acts as a compensatory mechanism to maintain SV in patients with severe HF.

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“…Cabe destacar que una de las medidas más significativas en su terapia fue haber recibido infusión IV de levosimendan, lo que a la luz de los hallazgos posteriores, se explica al recibir un sensibilizador al calcio junto con aporte de calcio administrado IV a raíz de hipocalcemia demostrada en ese instante. Levosimendán potencia la sensibilidad al calcio de los miofilamentos al unirse a la troponina C cardíaca, por un mecanismo dependiente del calcio, lo cual modifica la cinética de uniones cruzadas de la actina miosina sin afectar aparentemente a la tasa cíclica de uniones cruzadas ni al consumo miocárdico de ATP 21 . Aumenta la fuerza de contracción, pero sin afectar a la relajación ventricular, debido a la menor afinidad de unión cuando las concentraciones citosólicas de calcio se reducen durante la diástole.…”

Section: Discussionunclassified

Miocardiopatía por hipocalcemia

Johnson¹,

Toloza²,

Cortés³

et al. 2010

Rev Chil Cardiol

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Resumen:Se presenta el caso de un varón de 56 años, portador de Miocardiopatía dilatada, considerada, en algún momento, como terminal. Se comprobó que presentaba de base una hipocalcemia crónica secundaria a hipoparatiroidismo. Se discute su notable respuesta a administración de calcio e infusión de levosimendan IV fármaco inótropo positivo que actúa sensibilizando al calcio. Caso clínico FC 23456Paciente hombre de 54 años, el año 2005 estando asintomático se constata cardiomegalia en Rx tx ,durante una evaluación preoperatoria para intervención de cataratas. Se realiza ecocardiograma que mostró dilatación biventricular, signos de hipertensión pulmonar, dilatación auricular izquierda, insuficiencia mitral moderada y compromiso importante de la fracción de eyección, confirmando una miocardiopatía Dilatada (figuras 1 y 2) Evoluciona sintomático, con deterioro progresivo de la capacidad funcional, requiriendo hospitalizaciones frecuentes durante el año 2005 (en cuatro oportunidades). En febrero del 2006 se le realizó estudio coronariográfico que descartó enfermedad coronaria. Ese año es hospitalizado en forma reiterada (6 veces), evaluado como terminal, se le plantea la posibilidad de trasplante cardíaco, recibiendo infusiones de Dobutamina IV. En Mayo durante una hospitalización se detecta Fibrilación auricular y niveles bajos de calcemia iniciando terapia con gluconato de calcio IV.

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Levosimedan improves hemodynamics functions without sympathetic activation in severe heart failure patients: Direct evidence from sympathetic neural recording

Cited by 12 publications

References 26 publications

Pharmacology of levosimendan: inotropic, vasodilatory and cardioprotective effects

Pharmacology of levosimendan: inotropic, vasodilatory and cardioprotective effects

Relationship of stroke volume to different patterns of Cheyne-Stokes respiration in heart failure

Miocardiopatía por hipocalcemia

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