Efficacy and safety of nesiritide in patients with decompensated heart failure: a meta-analysis of randomised trials.

OBJECTIVES: Current evidence suggests that nesiritide may have effects on renal function and decrease the incidence of mortality. However, a clear superiority using nesiritide in terms of renal toxicity and mortality in patients with heart failure was not consistently proven by previous studies. We performed a meta-analysis of all randomised trials to obtain the best estimates of efficacy and safety of nesiritide for the initial treatment of decompensated heart failure. METHOD: We performed a meta-analysis of randomised trials of nesiritide in patients with decompensated heart failure (n=38,064 patients, in 22 trials). Two reviewers independently extracted data. Data on efficacy and safety outcomes were collected. We calculated pooled relatives risk (RRs), weighted mean difference and associated 95% CIs. RESULTS: Compared with placebo, dobutamine and nitroglycerin, nesiritide indicated no increasing risk of total mortality. Compared with the combined control therapy, nesiritide was associated with non-significant differences in short-term mortality (RR 1.24; 95% CI 0.85 to 1.80; p=0.27), mid-term mortality (RR 0.86; 95% CI 0.60 to 1.24; p=0.42) and long-term mortality (RR 0.94; 95% CI 0.75 to 1.18; p=0.61). Nesiritide therapy increased the risk of hypotension (p<0.00 001) and bradycardia (p=0.02) when compared with control therapy. Compared with dobutamine or placebo therapy, no differences in serum creatinine, blood urea nitrogen and creatinine clearance, and no risk of the need for dialysis was observed in nesiritide therapy. CONCLUSIONS: Our findings indicated that, in patients with heart failure, nesiritide was not associated with the risk of mortality. However, it increased the risk of cardiovascular adverse events. The change of serum creatinine and creatinine clearance had no significant difference, and no risk of the need for dialysis was observed after low-dose nesiritide treatment.

Total Mortality, Major Adverse Cardiac Events, and Echocardiographic-Derived Cardiac Parameters with Fragmented QRS Complex.

BACKGROUND: Fragmented QRS complex (fQRS), an easily evaluated noninvasive electrocardiographic parameter, is associated with worse outcomes in patients with several cardiovascular conditions. The presence of fQRS on ECG may be an indicator of myocardial damage in patients with coronary artery disease (CAD). In this article, we performed a meta-analysis in order to characterize the presence of fQRS on ECG in patients with CAD. METHODS: We searched English-language randomized controlled trials involving fQRS on ECG in patients with CAD (n = 3279 patients, 12 trials). Two reviewers independently extracted data. Data on LVEF, LVESD, LVEDD, LVESV, LVEDV, total mortality, stroke, and MACE were collected. fQRS was performed a comparison with non-fQRS, calculating pooled relatives risk (RRs) and weighted mean difference (WMD), and associated 95% confidence intervals (CIs). RESULTS: fQRS was associated with significant increased WMD of LVEDD (WMD, 2.26; 95%CI, 0.92 to 0.36, P = 0.0009), LVESD (WMD, 2.71; 95%CI, 1.23 to 4.19, P = 0.0003), LVEDV (WMD, 31.37; 95%CI, 24.82 to 37.92, P < 0.00001), and LVESV (WMD, 28.45; 95%CI, 22.92 to 33.98, P < 0.00001). As compared to non-fQRS, fQRS increased risk of total mortality (RR, 3.09; 95%CI, 1.76 to 5.44, P < 0.0001) and MACE (RR, 2.85; 95%CI, 1.98 to 4.09, P < 0.00001) in patients with CAD. However, a decreased trend was observed for LVEF (WMD, -3.59; 95%CI, -7.05 to -0.12, P = 0.04). For the incidence of stoke, there was no difference between fQRS and non-fQRS group. CONCLUSIONS: Our findings indicate that fQRS is a valuable factor to predict total mortality and MACE in patients with CAD.

Levosimendan Treatment for Heart Failure: A Systematic Review and Meta-Analysis.

OBJECTIVE: Emerging studies suggest that administration of levosimendan therapy may be better than dobutamine or placebo in decompensated heart failure. The authors performed an updated meta-analysis of trials to obtain the best estimates of the efficacy and safety of levosimendan for the initial treatment of decompensated heart failure. DESIGN: A meta-analysis. SETTING: Hospitals. PARTICIPANTS: A total of 5,349 patients from 25 randomized controlled studies were included in the analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors performed a meta-analysis of trials comparing levosimendan therapy with dobutamine or placebo in patients with decompensated heart failure. Twenty-five trials, involving 5,349 patients, were included. Two reviewers performed independent article review and study quality assessment. Data on overall mortality, early-term mortality, midterm mortality, long-term mortality, efficacy outcomes, and adverse events were collected. Mortality outcomes were according to follow-up duration: early term (≤30-day), midterm (30-day to≤6-month), and long term (>6-month). Levosimendan was compared with dobutamine or placebo, calculating pooled relatives risk (RRs) and associated 95% confidence intervals (CIs). A random-effects model was selected for meta-analysis if there was significant heterogeneity. Levosimendan significantly reduced total mortality (17.1% versus 20.8%; RR, 0.84; 95% CI, 0.75-0.94). Compared with dobutamine, levosimendan was associated with significant reduction in mortality at final follow-up (RR, 0.86; 95% CI, 0.76-0.97; I(2) = 7%; p = 0.02).Compared with placebo, levosimendan was associated with a nonsignificant trend in favor of placebo in mortality at final follow-up (11.6% versus 16.2%, RR, 0.75; 95% CI, 0.56-1.01; p = 0.06), but it was associated with a significant reduction in long-term mortality (RR, 0.34; 95%CI, 0.15-0.76; p = 0.009). Compared with dobutamine or placebo, levosimendan therapy was associated with improvements in hemodynamically- and echocardiographically-derived cardiac parameters. Levosimendan therapy increased the risks of extrasystoles (RR, 1.88; 95% CI, 1.26-2.81), hypotension (RR, 1.33; 95% CI, 1.15-1.53), and headache or migraine (RR, 1.94; 95% CI, 1.54-2.43) when compared with control therapy. CONCLUSIONS: As compared to placebo or dobutamine, levosimendan in patients with heart failure seemed to have hemodynamic and cardiac benefits. It reduced total mortality and was associated with an increased risk of cardiovascular adverse events.

Effects of low-level autonomic stimulation on prevention of atrial fibrillation induced by acute electrical remodeling.

BACKGROUND: Rapid atrial pacing (RAP) can induce electrical and autonomic remodeling and facilitate atrial fibrillation (AF). Recent reports showed that low-level vagosympathetic nerve stimulation (LLVNS) can suppress AF, as an antiarrhythmic effect. We hypothesized that LLVNS can reverse substrate heterogeneity induced by RAP. METHODS AND RESULTS: Mongrel dogs were divided into (LLVNS+RAP) and RAP groups. Electrode catheters were sutured to multiple atrial sites, and LLVNS was applied to cervical vagosympathetic trunks with voltage 50% below the threshold slowing sinus rate by ≤ 30 msec. RAP induced a significant decrease in effective refractory period (ERP) and increase in the window of vulnerability at all sites, characterized by descending and elevated gradient differences towards the ganglionic plexi (GP) sites, respectively. The ERP dispersion was obviously enlarged by RAP and more significant when the ERP of GP-related sites was considered. Recovery time from AF was also prolonged significantly as a result of RAP. LLVNS could reverse all these changes induced by RAP and recover the heterogeneous substrate to baseline. Conclusions. LLVNS can reverse the electrical and autonomic remodeling and abolish the GP-central gradient differences induced by RAP, and thus it can recover the homogeneous substrate, which may be the underlying mechanism of its antiarrhythmic effect.