Effects of Levosimendan on Left Ventricular Relaxation and Early Filling at Maintained Preload and Afterload Conditions After Aortic Valve Replacement for Aortic Stenosis

Jörgensen, Kirsten; Bech‐Hanssen, Odd; Houltz, Erik; Ricksten, Sven‐Erik

doi:10.1161/circulationaha.107.722868

Cited by 78 publications

(65 citation statements)

References 35 publications

(33 reference statements)

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“…The placebo effect may have affected the degree of the positive effect of a single‐dose levosimendan but cannot explain the whole effect. In uncontrolled settings, a placebo effect cannot be ruled out, but in prior randomized trials, placebo has not affected CO or stroke volume 28, 32…”

Section: Discussionmentioning

confidence: 99%

Haemodynamic effects of levosimendan in advanced but stable chronic heart failure

et al. 2018

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AimsLevosimendan improves haemodynamics in acute decompensated heart failure (HF). However, it is increasingly used for repetitive or intermittent infusions in advanced but stable chronic HF, without clear indication, selection criteria, or effect. We tested the hypotheses that (1) levosimendan improves haemodynamics in stable chronic HF and (2) that the response is dependent on baseline clinical and haemodynamic factors.Methods and resultsTwenty‐three patients [median age 56 (49–64) years, four (17%) women] with stable New York Heart Association (NYHA) III and IV HF received a single 24 h levosimendan infusion. Non‐invasive haemodynamics (inert gas re‐breathing technique), estimated glomerular filtration rate, and N‐terminal pro‐brain natriuretic peptide were assessed before and after infusion. Levosimendan had the following effects (median change): a significant increase in cardiac output (+9.8 ± 21.6%; P = 0.026) and decrease in N‐terminal pro‐brain natriuretic peptide (−28.1 ± 16.3%, P < 0.001), estimated total peripheral resistance (−16.9 ± 18.3%, P = 0.005), and mean arterial pressure (−5.9 ± 8.2%, P = 0.007), but no change in estimated glomerular filtration rate (+0.89 ± 14.0%, P = 0.955). There were no significant associations between baseline clinical and/or haemodynamic factors and the levosimendan effect on cardiac output.ConclusionsLevosimendan was associated with improved haemodynamics in patients with stable chronic HF, but we could not identify any predictors of the magnitude of haemodynamic response.

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Section: Discussionmentioning

confidence: 99%

Haemodynamic effects of levosimendan in advanced but stable chronic heart failure

et al. 2018

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“…Adenoviral gene transfer of SERCA-2A and modified phospholamban in animal models resulted in improved LV relaxation and diastolic function [53,145]. Levosimendan -a calcium channel sensitizer approved in Europe for IV use in acute heart failure -has also been shown to improve diastolic function in a recent small prospective randomized study [146].…”

Section: Future Directions and Emerging Therapiesmentioning

confidence: 99%

Heart Failure with Preserved Ejection Fraction

Čulić

2017

N Engl J Med

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Heart failure with preserved ejection fraction (HFpEF) has recently emerged as a major cause of cardiovascular morbidity and mortality. Contrary to initial beliefs, HFpEF is now known to be as common as heart failure with reduced ejection fraction (HFrEF) and carries an unacceptably high mortality rate. With a prevalence that has been steadily rising over the past two decades, it is very likely that HFpEF will represent the dominant heart failure phenotype over the coming few years. The scarcity of trials in this semi-discrete form of heart failure and lack of unified enrolment criteria in the studies conducted to date might have contributed to the current absence of specific therapies. Understanding the epidemiological, pathophysiological and molecular differences (and similarities) between these two forms of heart failure is cornerstone to the development of targeted therapies. Carefully designed studies that adhere to unified diagnostic criteria with the recruitment of appropriate controls and adoption of practical end-points are urgently needed to help identify effective treatment strategies.

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“…Levosimendan activates the opening of ATP-sensitive K + channels of smooth muscle cells allowing their hyperpolarization by leveraging vasodilation [24,25]. These vasodilatory properties lead to a dramatic increase in cardiac output with a concomitant reduction in cardiac filling pressures in the failing heart to enable it to generate more efficient systolic and diastolic functions [26,27]. All these mechanisms mentioned above may contribute to more rapid improvement of ventricular functions and clinical recovery in patients who were treated with levosimendan in this study.…”

Section: Discussionmentioning

confidence: 77%