An electrographic AV optimization for the maximum integrative atrioventricular and ventricular resynchronization in CRT.

BACKGROUND: Atrioventricular (AV) delay could affect AV and ventricular synchrony in cardiac resynchronization therapy (CRT). Strategies to optimize AV delay according to optimal AV synchrony (AVopt-AV) or ventricular synchrony (AVopt-V) would potentially be discordant. This study aimed to explore a new AV delay optimization algorithm guided by electrograms to obtain the maximum integrative effects of AV and ventricular resynchronization (opt-AV). METHODS: Forty-nine patients with CRT were enrolled. AVopt-AV was measured through the Ritter method. AVopt-V was obtained by yielding the narrowest QRS. The opt-AV was considered to be AVopt-AV or AVopt-V when their difference was < 20 ms, and to be the AV delay with the maximal aortic velocity-time integral between AVopt-AV and AVopt-V when their difference was > 20 ms. RESULTS: The results showed that sensing/pacing AVopt-AV (SAVopt-AV/PAVopt-AV) were correlated with atrial activation time (Pend-As/Pend-Ap) (P < 0.05). Sensing/pacing AVopt-V (SAVopt-V/PAVopt-V) was correlated with the intrinsic AV conduction time (As-Vs/Ap-Vs) (P < 0.01). The percentages of patients with more than 20 ms differences between SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V were 62.9% and 57.1%, respectively. Among them, opt-AV was linearly correlated with SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V. The sensing opt-AV (opt-SAV) = 0.1 × SAVopt-AV + 0.4 × SAVopt-V + 70 ms (R2 = 0.665, P < 0.01) and the pacing opt-AV (opt-PAV) = 0.25 × PAVopt-AV + 0.5 × PAVopt-V + 30 ms (R2 = 0.560, P < 0.01). CONCLUSION: The SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V were correlated with the atrial activation time and the intrinsic AV conduction interval respectively. Almost half of the patients had a > 20 ms difference between SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V. The opt-AV could be estimated based on electrogram parameters.

Acute Effects of Multisite Biventricular Pacing on Dyssynchrony and Hemodynamics in Canines With Heart Failure.

BACKGROUND: Multisite biventricular pacing (MSP) has been proposed as an alternative strategy to improve the efficiency of conventional biventricular pacing (BVP), but its utility remains unclear. This study sought to investigate whether MSP induced better synchrony and hemodynamic effects in canines with heart failure. METHODS AND RESULTS: After 3 weeks' rapid right ventricular pacing, 7 canines were sutured with 4 left ventricular (LV) leads on the anterior, lateral, posterior, and apical walls and followed by MSP and BVP. Hemodynamic, electrocardiographic, and echocardiographic parameters were measured. Dyssynchrony was assessed by tissue Doppler imaging for Yu-index (longitudinal direction) and speckle tracking imaging for the standard deviation of time to peak radial strains (SDε, radial direction). Compared with BVP, mean MSP reduced QRS width (P < .05), Yu-index (25.3 ± 1.9 ms vs 31.6 ± 4.3 ms, P = .008), SDε (32.8 ± 5.9 ms vs 37.3 ± 7.9 ms, P = .032), and LV end-diastolic pressure (P < .05). The optimal pacing site combination improved QRS width, Yu-index, SDε, LV end-diastolic pressure, and the maximum derivative of LV pressure (dP/dtmax) significantly (all P < .05), but the worst MSP (with the smallest dP/dtmax) did not show any improvement to BVP. CONCLUSIONS: MSP is superior to BVP in reducing dyssynchrony and improving hemodynamics. The pacing site combination has a potential effect on MSP response.

Short-term intensive atorvastatin therapy improves endothelial function partly via attenuating perivascular adipose tissue inflammation through 5-lipoxygenase pathway in hyperlipidemic rabbits.

BACKGROUND: Atherosclerosis is a kind of disease with multiple risk factors, of which hyperlipidemia is a major classical risk factor resulting in its pathogenesis and development. The aim of this study was to determine the effects of short-term intensive atorvastatin (IA) therapy on vascular endothelial function and explore the possible mechanisms that may help to explain the clinical benefits from short-term intensive statin therapy. METHODS: After exposure to high-fat diet (HFD) for 8 weeks, the animals were, respectively, treated with IA or low-dose atorvastatin (LA) for 5 days. Blood lipids, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), endothelin-1 (ET-1), and endothelium-dependent vasorelaxation function were, respectively, measured. mRNA and protein expression of CRP, TNF-α, IL-6, macrophage chemoattractant protein-1 (MCP-1), and 5-lipoxygenase (5-LO) were also evaluated in pericarotid adipose tissue (PCAT) and cultured adipocytes. RESULTS: HFD increased serum inflammatory factor levels; induced significant hyperlipidemia and endothelial dysfunction, including imbalance between NO and ET-1; enhanced inflammatory factors and 5-LO expression; and promoted macrophage infiltration into adipose tissue. Five-day IA therapy could significantly decrease serum inflammatory factor levels and their expression in PCAT; restore the balance between NO and ET-1; and improve endothelial function and macrophage infiltration without significant changes in blood lipids. However, all of the above were not observed in LA therapy. In vitro experiment found that lipopolysaccharide (LPS) enhanced the expression of inflammatory factors and 5-LO in cultured adipocytes, which could be attenuated by short-time (6 hours) treatment of high-dose (5 µmol/L) but not low-dose (0.5 µmol/L) atorvastatin. In addition, inhibiting 5-LO by Cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC, a potent and direct 5-LO inhibitor) could significantly downregulate the above-mentioned gene expression in LPS-treated adipocytes. CONCLUSION: Short-term IA therapy could significantly ameliorate endothelial dysfunction induced by HFD, which may be partly due to attenuating inflammation of PCAT through inhibiting 5-LO pathway.

Tumor necrosis factor-alpha G-308A gene polymorphism and coronary heart disease susceptibility: an updated meta-analysis.

PURPOSE: Several studies have reported apparently conflicting findings for the effects of tumor necrosis factor-alpha (TNF-α) G-308A polymorphism on coronary heart disease (CHD) susceptibility. We undertook a systematic review and meta-analysis to investigate the association between this gene variant and CHD predisposition. METHODS: We systematically searched electronic databases (Medline, EMbase, Chinese BioMedical, BIOSIS, Global Health, PsycINFO, Allied and Complementary Medicine Database, Cochrane Library, HuGE Navigator, and British Nursing) for relevant studies published between 1947 and October, 2010. Summarized estimation of odds ratio (OR) and 95% confidence interval (CI) were calculated. Publication bias and heterogeneity among studies were explored. RESULTS: We identified 24 studies providing data for 9 921 cases and 7 944 controls. Pooled analysis based on ORs adjusted by CHD risk factors showed that carrying the TNF-α gene A variant conferred a 1.5-fold increased risk of developing CHD (AG+AA vs. GG, OR = 1.50, 95% CI: 1.23-1.77) in Caucasian population. No significant association between the gene polymorphism and CHD risk could be found in other ethnic groups. CONCLUSIONS: It is probable that carrying the A variant is associated with CHD risk in Caucasians but not in Asians, Indians, or Africans. Further studies are merited to assess the association in greater details, especially in Asians, Indians and Africans.

Endogenous pro-resolving and anti-inflammatory lipid mediators: the new hope of atherosclerotic diseases.

Atherosclerosis is a complex disease process in which genetic, lipid, cellular, and immunological factors combine to determine the location, severity, and timing of lesion development and clinical events. It has been demonstrated, however, that inflammation governed atherosclerosis during the course of development of atherosclerosis. It has also been demonstrated to be effective to decrease the cardiovascular events and improve the prognosis of atherosclerotic diseases by regulating inflammatory reaction (e.g., statins). However, endogenous mechanisms of limiting inflammation in atherosclerosis are still unclear. Recent studies showed that lipoxidase/leukotrienes (LOX/LTs) pathway played important role in the ignition and development of atherosclerosis, whereas resolvins (E-series resolvins and D-series resolvins) and protectins [protectin D1 (PD1) and neuroprotectin D1 (NPD1)], endogenous lipid-derived mediators, inhibited inflammation through pro-resolution and counter-modulating immune inflammation reaction in atherosclerosis. Hence, we hypothesize that increased endogenous lipid mediators mentioned above play a vital role in anti-atherosclerosis and plaque stabilization through pro-resolution and anti-inflammation by LOX/LTs pathway. In addition, we predict that the endogenous lipid mediators may be a new target for treatment of atherosclerotic diseases.