| 1. |
- Poelzl, Gerhard, et al.
(author)
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Repetitive levosimendan infusions for patients with advanced chronic heart failure in the vulnerable post-discharge period : The multinational randomized LeoDOR trial
- 2023
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In: European Journal of Heart Failure. - : John Wiley & Sons. - 1388-9842 .- 1879-0844. ; 25:11, s. 2007-2017
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Journal article (peer-reviewed)abstract
- Aim The LeoDOR trial explored the efficacy and safety of intermittent levosimendan therapy in the vulnerable phase following a hospitalization for acute heart failure (HF) Methods and results In this prospective multicentre, double-blind, two-armed trial, patients with advanced HF were randomized 2:1 at the end of an index hospitalization for acute HF to intermittent levosimendan therapy or matching placebo for 12weeks. All patients had left ventricular ejection fraction (LVEF) =30% during index hospitalization. Levosimendan was administered according to centre preference either as 6 h infusion at a rate of 0.2 mu g/kg/min every 2weeks, or as 24 h infusion at a rate of 0.1 mu g/kg/min every 3weeks. The primary efficacy assessment after 14weeks was based on a global rank score consisting of three hierarchical groups. Secondary clinical endpoints included the composite risk of tiers 1 and 2 at 14 and 26weeks, respectively. Due to the COVID-19 pandemic, the planned number of patients could not be recruited. The final modified intention-to-treat analysis included 145 patients (93 in the combined levosimendan arm, 52 in the placebo arm), which reduced the statistical power to detect a 20% risk reduction in the primary endpoint to 60%. Compared with placebo, intermittent levosimendan had no significant effect on the primary endpoint: the mean rank score was 72.55 for the levosimendan group versus 73.81 for the placebo group (p= 0.863). However, there was a signal towards a higher incidence of the individual clinical components of the primary endpoint in the levosimendan group versus the placebo group both after 14weeks (hazard ratio [HR] 2.94, 95% confidence interval [CI] 1.12- 7.68; p= 0.021) and 26weeks (HR 1.64, 95% CI 0.87- 3.11; p= 0.122). Among patients recently hospitalized with HF and reduced LVEF, intermittent levosimendan therapy did not improve post-hospitalization clinical stability. [GRAPHICS.]
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| 2. |
- Poelzl, Gerhard, et al.
(author)
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Repetitive use of levosimendan in advanced heart failure : need for stronger evidence in a field in dire need of a useful therapy
- 2017
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In: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 243, s. 389-395
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Journal article (peer-reviewed)abstract
- Patients in the latest stages of heart failure are severely compromised, with poor quality of life and frequent hospitalizations. Heart transplantation and left ventricular assist device implantation are viable options only for a minority, and intermittent or continuous infusions of positive inotropes may be needed as a bridge therapy or as a symptomatic approach. In these settings, levosimendan has potential advantages over conventional inotropes (catecholamines and phosphodiesterase inhibitors), such as sustained effects after initial infusion, synergy with beta-blockers, and no increase in oxygen consumption. Levosimendan has been suggested as a treatment that reduces re-hospitalization and improves quality of life. However, previous clinical studies of intermittent infusions of levosimendan were not powered to show statistical significance on key outcome parameters. A panel of 45 expert clinicians from 12 European countries met in Rome on November 24-25, 2016 to review the literature and envision an appropriately designed clinical trial addressing these needs. In the earlier FIGHT trial (daily subcutaneous injection of liraglutide in heart failure patients with reduced ejection fraction) a composite Global Rank Score was used as primary end-point where death, re-hospitalization, and change in N-terminalprohormone-brain natriuretic peptide level were considered in a hierarchical order. In the present study, we tested the same end-point post hoc in the PERSIST and LEVOREP trials on oral and repeated i.v. levosimendan, respectively, and demonstrated superiority of levosimendan treatment vs placebo. The use of the same composite end-point in a properly powered study on repetitive levosimendan in advanced heart failure is strongly advocated.
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| 3. |
- Pölzl, Gerhard, et al.
(author)
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Repetitive levosimendan infusions for patients with advanced chronic heart failure in the vulnerable post-discharge period
- 2019
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In: ESC Heart Failure. - : WILEY PERIODICALS, INC. - 2055-5822. ; 6:1, s. 174-181
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Journal article (peer-reviewed)abstract
- Hospitalization for acute heart failure (HF) is associated with a substantial morbidity burden and with associated healthcare costs and an increased mortality risk. However, few if any major medical innovations have been witnessed in this area in recent times. Levosimendan is a first-in-class calcium sensitizer and potassium channel opener indicated for the management of acute HF. Experience in several clinical studies has indicated that administration of intravenous levosimendan in intermittent cycles may reduce hospitalization and mortality rates in patients with advanced HF; however, none of those trials were designed or powered to give conclusive insights into that possibility. This paper describes the rationale and protocol of LeoDOR (levosimendan infusions for patients with advanced chronic heart failure), a randomized, double-blind, placebo-controlled, international, multicentre trial that will explore the efficacy and safety of intermittent levosimendan therapy, in addition to optimized standard therapy, in patients following hospitalization for acute HF. Salient features of LeoDOR include the use of two treatment regimens, in order to evaluate the effects of different schedules and doses of levosimendan during a 12 week treatment phase, and the use of a global rank primary endpoint, in which all patients are ranked across three hierarchical groups ranging from time to death or urgent heart transplantation or implantation of a ventricular assist device to time to rehospitalization and, lastly, time-averaged proportional change in N-terminal pro-brain natriuretic peptide. Secondary endpoints include changes in HF symptoms and functional status at 14 weeks.
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| 4. |
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| 5. |
- Alayon Glazunov, Andres, et al.
(author)
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On the mean effective gain expressed in terms of the spherical vector wave expansion of the electromagnetic field
- 2008
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Conference paper (peer-reviewed)abstract
- The mode expansion o®ers a general framework for the analysis of the interaction between antennas andpropagation channels. In this paper, the Mean E®ective Gain (MEG) of an antenna is expressed in termsof the spherical vector wave expansion of the electromagnetic ¯eld. An explicit expression of the MEG isprovided as a function of the normalized average power of modes excited in the propagation channel andthe correlation between the channel modes due to the polarization and spatial selectivity of plane wavesimpinging at the antenna.
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| 6. |
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| 7. |
- Alayon Glazunov, Andres, et al.
(author)
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Spherical Vector Wave Expansion of Gaussian Electromagnetic Fields for Antenna-Channel Interaction Analysis
- 2009
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In: IEEE Transactions on Antennas and Propagation. - 0018-926X .- 1558-2221. ; 57:7, s. 2055-2067
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Journal article (peer-reviewed)abstract
- In this paper, we introduce an approach to analyze the interaction between antennas and the propagation channel. We study both the antennas and the propagation channel by means of the spherical vector wave mode expansion of the electromagnetic field. Then we use the expansion coefficients to study some properties of general antennas in thosefields by means of the antenna scattering matrix. The focus is on the spatio-polar characterization of antennas, channels and their interactions. We provide closed form expressions for the covariance of the field multimodes as function of the power angle spectrum (PAS) and the channel cross-polarization ratio (XPR). A new interpretation of the mean effective gains (MEG) of antennas is also provided. The maximum MEG is obtained by conjugate mode matching between the antennas and the channel; we also prove the (intuitive) results that the optimum decorrelation of the antenna signals is obtained by the excitation of orthogonal spherical vector modes.
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| 8. |
- Alayon Glazunov, Andres, et al.
(author)
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Spherical Vector Wave Expansion of Gaussian Electromagnetic Fields for Antenna-Channel Interaction Analysis
- 2008
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Reports (other academic/artistic)abstract
- In this paper we introduce an approach to analyze the interaction between antennas and the propagation channel. We study both the antennas and the propagation channel by means of the spherical vector wave mode expansion of the electromagnetic field. Then we use the expansion coefficients to study some properties of general antennas in those fields by means of the antenna scattering matrix. The focus is on the spatio-polar characterization of antennas, channels and their interactions. We provide closed form expressions for the covariance of the field multi-modes as function of the Power Angle Spectrum (PAS) and the channel cross-polarization ratio (XPR). A new interpretation of the Mean Effective Gains (MEG) of antennas is also provided. The maximum MEG is obtained by conjugate mode matching between the antennas and the channel; we also prove the (intuitive) results that the optimum decorrelation of the antenna signals is obtained by the excitation of orthogonal spherical vector modes.
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