Effect of levosimendan on ventricular remodelling in patients with left ventricular systolic dysfunction: a meta-analysis

Abstract

Heart failure is the final stage of several cardiovascular diseases, and the key to effectively treating heart failure is to reverse or delay ventricular remodelling. Levosimendan is a novel inotropic and vasodilator agent used in heart failure, whereas the impact of levosimendan on ventricular remodelling is still unclear. This study aims to investigate the impact of levosimendan on ventricular remodelling in patients with left ventricular systolic dysfunction. Electronic databases were searched to identify eligible studies. A total of 66 randomized controlled trials involving 7968 patients were included. Meta-analysis results showed that levosimendan increased left ventricular ejection fraction [mean difference (MD) = 3.62, 95% confidence interval (CI) (2.88, 4.35), P < 0.00001] and stroke volume [MD = 6.59, 95% CI (3.22, 9.96), P = 0.0001] and significantly reduced left ventricular end-systolic volume [standard mean difference (SMD) = -0.52, 95% CI (-0.67, -0.37), P < 0.00001], left ventricular end-diastolic volume index [SMD = -1.24, 95% CI (-1.61, -0.86), P < 0.00001], and left ventricular end-systolic volume index [SMD = -1.06, 95% CI (-1.43, -0.70), P < 0.00001]. In terms of biomarkers, levosimendan significantly reduced the level of brain natriuretic peptide [SMD = -1.08, 95% CI (-1.60, -0.56), P < 0.0001], N-terminal pro-brain natriuretic peptide [SMD = -0.99, 95% CI (-1.41, -0.56), P < 0.00001], and interleukin-6 [SMD = -0.61, 95% CI (-0.86, -0.35), P < 0.00001]. Meanwhile, levosimendan may increase the incidence of hypotension [risk ratio (RR) = 1.24, 95% CI (1.12, 1.39), P < 0.0001], hypokalaemia [RR = 1.57, 95% CI (1.08, 2.28), P = 0.02], headache [RR = 1.89, 95% CI (1.50, 2.39), P < 0.00001], atrial fibrillation [RR = 1.31, 95% CI (1.12, 1.52), P = 0.0005], and premature ventricular complexes [RR = 1.86, 95% CI (1.27, 2.72), P = 0.001]. In addition, levosimendan reduced all-cause mortality [RR = 0.83, 95% CI (0.74, 0.94), P = 0.002]. In conclusion, our study found that levosimendan might reverse ventricular remodelling when applied in patients with left ventricular systolic dysfunction, especially in patients undergoing cardiac surgery, decompensated heart failure, and septic shock.

Keywords: Left ventricular systolic dysfunction; Levosimendan; Meta‐analysis; Safety; Ventricular remodelling.

Figure 1

Flow chart of literature screening for this meta‐analysis. RCT, randomized controlled trial.

Figure 2

Meta‐analysis results of (A) left ventricular end‐diastolic diameter (LVEDD) and (B) left ventricular end‐systolic diameter (LVESD). CI, confidence interval; IV, inverse variance; SD, standard deviation.

Figure 3

Meta‐analysis results of (A) left ventricular end‐diastolic volume (LVEDV), (B) left ventricular end‐diastolic volume index (LVEDVI), (C) left ventricular end‐systolic volume (LVESV), and (D) left ventricular end‐systolic volume index (LVESVI). CI, confidence interval; IV, inverse variance; SD, standard deviation.

Figure 4

Meta‐analysis results of (A) left ventricular ejection fraction (LVEF) and (B) stroke volume (SV). CI, confidence interval; IV, inverse variance; SD, standard deviation.

Figure 5

Meta‐analysis results of (A) brain natriuretic peptide (BNP), (B) N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), and (C) interleukin‐6 (IL‐6). CI, confidence interval; IV, inverse variance; SD, standard deviation.

Figure 6

Meta‐analysis of all‐cause mortality. CI, confidence interval; M‐H, Mantel–Haenszel.

Figure 7

Meta‐analysis results of (A) hypotension, (B) hypokalaemia, (C) headache, and (D) atrial fibrillation. CI, confidence interval; IV, inverse variance; M‐H, Mantel–Haenszel.

Figure 8

Meta‐analysis results of (A) premature ventricular complexes, (B) sinus tachycardia, and (C) ventricular tachycardia. CI, confidence interval; M‐H, Mantel–Haenszel.

Figure 9

Funnel plot of publication bias of (A) left ventricular ejection fraction (LVEF), (B) left ventricular end‐systolic diameter (LVESD), (C) left ventricular end‐diastolic diameter (LVEDD), and (D) stroke volume (SV). se, standard error; WMD, weighted mean difference.

Figure 10

Funnel plot of publication bias of (A) brain natriuretic peptide (BNP), (B) mortality, (C) atrial fibrillation (AF), and (D) hypotension. rr or RR, risk ratio; se, standard error; SMD, standard mean difference.