The natural history of multifocal atrial rhythms in elderly outpatients: insights from the "Ikaria study".

BACKGROUND: Multifocal atrial tachycardias confer an adverse prognosis in hospitalized patients. We assessed the prognostic impact of multifocal atrial rhythms (MARs-either chaotic atrial rhythm or multifocal atrial tachycardia/bradycardia) in very elderly outpatients. METHODS: One hundred ten subjects aged 60-74 years, 112 aged 75-89 years, and 61 over 90 years old, were enrolled and prospectively evaluated. Several demographic and clinical characteristic were recorded in all individuals. RESULTS: A high prevalence of MARs was detected in the study population (namely, 6%), which in subjects >90 years was even higher (15%). Individuals with MARs were older, more often female and less active. In multivariate analysis, independent predictors of MARs were age (OR = 1.07, 95% CI: 1.02-1.13, P = 0.01) and female sex (OR = 4.77, 95% CI: 1.23-18.48, P = 0.02). The mortality rate during the follow-up period was 8.4% without differences between age groups (P = 0.209). In particular, mortality rate was 6% in individuals with MARs and 9% in those without (P = 0.72). Mortality was associated with age (OR 1.07, 95% CI: 1.02-1.12, P = 0.005) and history of cardiovascular disease at baseline (OR 4.57, 95% CI: 1.87-11.2 P = 0.001). CONCLUSIONS: Contrary to hospitalized individuals with multifocal atrial tachycardias, MARs were not associated with increased mortality in elderly outpatients in this study.

Effect of gender on the prognostic value of dobutamine stress myocardial contrast echocardiography.

BACKGROUND: Dobutamine stress contrast echo (DSCE) has a well-established prognostic value in the context of coronary artery disease (CAD). However, data regarding its prognostic capability separately in men and women are scarce. The aim of the current study was to assess gender-related differences in the prognostic performance of DSCE. METHODS: DSCE was performed in 2645 consecutive patients, who were classified into two groups depending on gender. Follow-up lasted 57.1±10.1 months. End points included all-cause mortality, cardiac death, late revascularization, and hospitalizations. Survival analysis was performed comparing men and women. RESULTS: Of the 2645 patients (59.3±8.7 years), 69.1% were men. DSCE was positive in 23.4% of male patients, while in females, the respective percentage was 14.3%. There was statistically significant difference between the two groups with regard to end point occurrence (11.6% vs. 6.1%, p<0.05). Multivariate analysis revealed that the DSCE response was the strongest predictor of adverse outcomes (Exp(B)=51.9, p<0.05) in both groups. The predictive model including DSCE results along with clinical data performed well without significant differences between males and females (C-index 0.93 vs. 0.87 respectively, p=NS). CONCLUSION: DSCE has a strong prognostic value for patients with known or suspected CAD, regardless of patient gender. This makes DSCE an attractive screening option for women in whom CAD assessment can be challenging.

Effects of rosuvastatin on myeloperoxidase levels in patients with chronic heart failure: a randomized placebo-controlled study.

BACKGROUND: Studies indicate that myeloperoxidase (MPO) is associated with disease progression and severity in heart failure (HF), while it may provide a mechanistic link between inflammation and adverse cardiac remodeling. The mechanisms that regulate MPO are unclear, while it is unknown whether specific treatments such as HMG-CoA reductase inhibitors and xanthine oxidase inhibitors may modify MPO. Therefore in the present study we examined the effects of rosuvastatin and allopurinol on MPO levels in patients HF. METHODS: Sixty clinically stable patients with systolic HF were randomized to receive rosuvastatin 10mg/day, allopurinol 300mg/day or placebo and followed up for 1 month. Plasma levels of MPO and serum levels of soluble CD40 ligand, interleukin-6, and oxidized LDL were determined using ELISA. All measurements were made before and after 1-month treatment. RESULTS: Rosuvastatin significantly reduced plasma levels of MPO (p=0.003), which remained unchanged in the other groups. Furthermore, the change of MPO levels in the rosuvastatin-treated group was significantly different compared with the other groups (p<0.05). Rosuvastatin administration also led to a significant decrease in oxidized LDL (p=0.009), while the other inflammatory markers remained unchanged in all groups. In the total population, a significant correlation was observed between the baseline levels of MPO and hsCRP (r=0.275, p=0.027), fibrinogen (r=0.278, p=0.025), and sCD40L (r=0.288, p=0.021). CONCLUSIONS: Short-term treatment with rosuvastatin regulates inflammatory process in patients with heart failure by significantly reducing plasma levels of MPO. This finding reveals a novel pleiotropic effect of statins in patients with heart failure, and provides further insights into the pathophysiological mechanisms of MPO in heart failure.

Oxidative stress and inflammatory process in patients with atrial fibrillation: the role of left atrium distension.

BACKGROUND: Atrial fibrillation has been associated with increased oxidative stress, elevated inflammatory status and endothelial dysfunction. However, the underlying mechanisms regulating the expression of inflammatory markers or oxidative stress status are unclear. We searched for clinical determinants of oxidative stress status, endothelial function and inflammatory process in patients with chronic atrial fibrillation. METHODS: Sixty nine patients with chronic atrial fibrillation at a stable clinical state were recruited. Ejection fraction of the left ventricle and the dimensions of the left atrium were determined echocardiographically. Flow mediated dilatation (FMD) was evaluated in the brachial artery, while serum oxidized LDL (ox-LDL), matrix metalloproteinase-9 (MMP-9), soluble CD40-ligand (sCD40L) and C-reactive protein (CRP) were measured. RESULTS: FMD was correlated with CRP (r=-0.423, p=0.028), independently of other clinical parameters (beta(SE): -0.0039(0.00159), p=0.022). Ox-LDL was significantly correlated with left atrium diameter(r=0.358, p=0.005) independently of other clinical variables (beta(SE):1.288(0.455), p=0.007). The only independent predictors of MMP-9 were sCD40L (beta(SE):17.232(7.654), p=0.028), CRP (beta(SE):4.249(2.186), p=0.05) and gender (beta(SE):204.657(68.153), p=0.004), but not left atrium dimensions. Independent predictors of CRP were hypertension (beta(SE): 8.531(3.973), p=0.036), sCD40L (beta(SE): 0.779(0.408), p=0.06) and age (beta(SE): 0.381(0.201), p=0.063). CONCLUSIONS: There is a strong link between inflammation and endothelial function, in patients with atrial fibrillation. The maximum diameter of left atrium is the only independent predictor of oxidized LDL, suggesting that left atrium distension may predict oxidative stress status in these patients.

The impact of oral L-arginine supplementation on acute smoking-induced endothelial injury and arterial performance.

BACKGROUND: Smoking is associated with endothelial dysfunction and increased inflammatory status. The amino acid L-arginine, improves endothelial function in patients with cardiovascular risk factors. We investigated the effect of L-arginine on vascular function and inflammatory process in healthy smokers at rest and after acute smoking. METHODS: We studied the effect of L-arginine and/or placebo in 12 healthy young smokers on three occasions (day 0, day 1, and day 3). The study was carried out on two separate arms, one with L-arginine (3 x 7 g/day) and one with placebo, according to a randomized, placebo-controlled, double-blind, cross-over design. Measurements were carried out before, immediately after, and 20 min after cigarette smoking. Endothelial function was evaluated by flow-mediated dilation (FMD). Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) and as a measure of arterial wave reflections. Serum soluble intercellular adhesion molecule-1 (sICAM-1) was measured. RESULTS: Compared to placebo, L-arginine improved FMD (P < 0.01 at day 1 and P < 0.05 at day 3). L-Arginine reduced PWV and AIx at both days 1 and 3 (P < 0.05 vs. baseline). L-Arginine blunted the acute smoking-induced increase of AIx at both day 1 (P < 0.05) and day 3 (P < 0.01), and prevented the smoking-induced elevation of PWV at day 3 (P < 0.05). Importantly, L-arginine reduced sICAM-1 at days 1 and 3 (P < 0.05 for both vs. baseline). CONCLUSIONS: Oral L-arginine improves endothelial function and vascular elastic properties of the arterial tree during the acute phase of smoking, an effect accompanied by reduced sICAM-1 levels in these subjects.

Short-term treatment with L-arginine prevents the smoking-induced impairment of endothelial function and vascular elastic properties in young individuals.

BACKGROUND: L-arginine, the substrate for endothelial nitric oxide synthase, is essential for normal endothelial function. Aim of the present study was to investigate in healthy smokers the effect of a short-term daily L-arginine administration on vascular function. METHODS: We studied the effect of a 3-day oral administration of L-arginine in 10 healthy smokers (24.3+/-0.73 years old) on 3 occasions (day , day 1 and day 3). The study was carried out on two separate arms, one with L-arginine (7 gr/d) and one with placebo according to a randomized, placebo-controlled, double-blind, cross-over design. Measurements were carried out before, immediately after (Sm0) and 20 min after (Sm20) cigarette smoking. Endothelial function was evaluated by flow-mediated dilatation (FMD) of the brachial artery. Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AIx) as a measure of arterial wave reflections. RESULTS: Compared to placebo, L-arginine led to an increase of FMD (p<0.05 at day 2), indicating a favorable effect on endothelial function, which however lost significance at day 3. l-arginine induced a progressive decrease of PWV and AIx at both day 2 and day 3 (p<0.01 vs baseline for all). L-arginine blunted the acute smoking-induced increase of AIx at both day 1 (p<0.05) and day 3 (p<0.01), and there was a trend to protect the smoking-induced change of PWV at day 3 (p<0.1). CONCLUSIONS: Short-term daily administration of L-arginine improves arterial performance in healthy smokers and abrogates the smoking-induced increase in arterial stiffness and wave reflections in these individuals.