Surfactant proteins changes after acute hemodynamic improvement in patients with advanced chronic heart failure treated with Levosimendan

Abstract

Alveolar-capillary membrane evaluated by carbon monoxide diffusion (DLCO) plays an important role in heart failure (HF). Surfactant Proteins (SPs) have also been suggested as a worthwhile marker. In HF, Levosimendan improves pulmonary hemodynamics and reduces lung fluids but associated SPs and DLCO changes are unknown. Sixty-five advanced HF patients underwent spirometry, cardiopulmonary exercise test (CPET) and SPs determination before and after Levosimendan. Levosimendan caused natriuretic peptide-B (BNP) reduction, peakVO increase and VE/VCO slope reduction. Spirometry improved but DLCO did not. SP-A, SP-D and immature SP-B reduced (73.7 ± 25.3 vs. 66.3 ± 22.7 ng/mL*, 247 ± 121 vs. 223 ± 110 ng/mL*, 39.4 ± 18.7 vs. 34.4 ± 17.9AU*, respectively); while mature SP-B increased (424 ± 218 vs. 461 ± 243 ng/mL, * = p < 0.001). Spirometry, BNP and CPET changes suggest hemodynamic improvement and lung fluid reduction. SP-A, SP-D and immature SP-B reduction indicates a reduction of inflammatory stress; conversely mature SP-B increase suggests alveolar cell function restoration. In conclusion, acute lung fluid reduction is associated with SPs but not DLCO changes. SPs are fast responders to alveolar-capillary membrane condition changes.

Impact of Sacubitril/Valsartan on surfactant binding proteins, central sleep apneas, lung function tests and heart failure biomarkers: Hemodynamic or pleiotropism?

“…In chronic HF the alveolar capillary membrane dysfunction is associated with long-lasting pathophysiological mechanisms such as interstitial fibrosis, local thrombosis and an increased in cellularity on top of lung fluid increase. As previously described in other therapeutic settings (8,36,37), treatment with ultrafiltration or inotropes in acute HF patients, despite an important and rapid lung fluid reduction, opposite to lung mechanics, does not affect DLCO which remains unchanged even after hemodynamic amelioration (36,37,43,44). The same lack of improvement in lung membrane diffusing capacity is also observed following heart transplantation (45).…”

“…Importantly, its values respond to hemodynamics targeted HF treatments, such as infusion of Levosimendan in acute HF (8), suggesting that it may be useful in the evaluation of treatment responsiveness. Thus, also the reduction in circulating proSP-B levels in response to Sacubitril/Valsartan is conceivable with a hemodynamic improvement.…”

Sensitivity and specificity of different exercise oscillatory ventilation definitions to predict 2-year major adverse cardiovascular outcomes in chronic heart failure patients

“…CPETs followed the hospital routine [12]. Briefly, a personalized ramp protocol was performed on an electronically braked cycle ergometer (Erg 800S; Sensor Medics, Yorba Linda, CA) [5,13]. All subjects were instructed to perform a maximal effort (exercise peak near to10 min).…”

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use

“…85 Due to the large therapeutic field they encompass, the European guidelines on acute and chronic HF are not as detailed as they could be and, in recommending therapeutic agents, ignore some of the different aetiologies and manifestations of AHF. Supplementary information and recommendations can be found in more than 20 expert consensus papers co-authored by more than 180 clinicians from 30 countries who have discussed when and how to use levosimendan in different therapeutic settings, including AHF and cardiogenic shock, 74,81,[86][87][88] AdHF, [89][90][91][92] perioperative use, [93][94][95] and use in the intensive care unit (ICU), 96 and who have described its cardiorenal effects, 88,97 its effects on quality of life, 98,99 exercise performance, 100 lung function, 101 and pharmaco-economic considerations. 102 In the context of a 20-year retrospective it is worth noting at this point that its complex mode of action might have had the potential to disadvantage levosimendan both in fact and in perception.…”