RESUMO
Heart failure (HF) has been proposed as a potential indication of renal denervation (RDN). However, the mechanisms enabling RDN to attenuate HF are not well understood, especially the central effects of RDN. The aim of this study was to decipher the mode of operation of RDN in the treatment of HF using a canine model of right ventricular rapid pacing-induced HF. Accordingly, 24 Chinese Kunming dogs were randomly grouped to receive sham procedure (sham-operated group), bilateral RDN (RDN group), rapid pacing to induce HF (HF-control group), and bilateral RDN plus rapid pacing (RDN + HF group). Echocardiography, plasma brain natriuretic peptide (BNP), and norepinephrine (NE) concentrations of randomized dogs were measured at baseline and 4 weeks after interventions, followed by histological and molecular analyses. Twenty dogs completed the research successfully and were enrolled for data analyses. Results showed that the average optical density of renal efferent and afferent nerves were significantly lower in the RDN and RDN + HF groups than in the sham-operated group, with a significant reduction of renal NE concentration. Rapid pacing in the RDN + HF and HF-control groups, compared with the sham-operated group, induced a significant increase in left ventricular end-diastolic volume and decrease in left ventricular ejection fraction and correspondingly resulted in cardiac fibrosis and dysfunction. Cardiac fibrosis evaluated by Masson's trichrome staining and the expression of transforming growth factor-ß1 (TGF-ß1) were significantly higher in the HF-control group than in the sham-operated group, which were remarkably attenuated by the application of the RDN technique in the RDN + HF group. In terms of central renin-angiotensin system (RAS), the expression of angiotensin II (AngII)/angiotensin-converting enzyme (ACE)/AngII type 1 receptor (AT1R) in the hypothalamus of dogs in the HF-control group, compared with the sham-operated group, was upregulated and that of the angiotensin-(1-7) [Ang-(1-7)]/ACE2 was downregulated. Furthermore, both of them were significantly attenuated by the RDN therapy in the RDN + HF group. In conclusion, the RDN technique could damage renal nerves and suppress the cardiac remodeling procedure in canine with HF while concomitantly attenuating the overactivity of central RAS in the hypothalamus.
RESUMO
OBJECTIVE: The efficacy of rate and rhythm control strategies for treating atrial fibrillation (AF) patients was analyzed in this meta-analysis. METHODS: Eligible trials were searched in MEDLINE, the Cochrane Library, the Clinical Trials, the Chinese VIP database up to May 31, 2010. Ten prospective randomized control trials with 7876 patients (rate control n = 3932, rhythm control n = 3944) were included for final analysis. RESULTS: All cause mortality (5.3% vs. 5.0%; OR: 1.03; 95%CI: 0.84 - 1.26; I(2) < 25%) and incidence of worsening heart failure (3.81% vs. 3.61%; OR: 1.04; 95%CI: 0.80 - 1.36; I(2) < 50%) were similar between the two groups. Subgroup analysis showed that all cause mortality (3.6% vs.1.9%; OR: 1.89; 95%CI: 1.01 - 3.53; I(2) < 25%) and rate of worsening heart failure (2.3% vs. 0.3%; OR: 5.6; 95%CI: 1.44 - 21.69; I(2) < 25%) were significantly higher in rate control group than in rhythm control group in patients with age < 65 years. Thromboembolic events (1.49% vs. 1.46%; OR: 1.02, 95%CI: 0.71 - 1.48) and bleeding events (1.78% vs. 1.73%; OR: 1.02, 95%CI: 0.70 - 1.49) were similar between rhythm control and rate control groups while rehospitalization rate was significantly lower in rate control group than in rhythm control group (17.56% vs. 22.98%; OR: 0.37, 95%CI: 0.19 - 0.71). CONCLUSION: This meta-analysis shows that rhythm control strategy is superior to rate control strategy for AF patients with age < 65 years in terms of reducing all cause mortality and incidence of worsening heart failure.
