Predictors of the voltage derived left atrial fibrosis in patients with long-standing persistent atrial fibrillation

Background: Left atrial (LA) arrhythmogenic substrate beyond the pulmonary veins (PV) seems to play a crucial role in the maintenance of atrial fibrillation (AF). The aim of this study was to evaluate the association of selected parameters with the presence and extent of voltage-defined LA fibrosis in patients with long-standing persistent AF (LSPAF) undergoing catheter ablation. Methods: One hundred and sixteen consecutive patients underwent high density-high resolution voltage mapping of the LA with a multielectrode catheter following PV isolation and restoration of sinus rhythm with cardioversion. A non-invasive dataset, such as clinical variables, two-and three-dimensional echocardiography determined LA size and function and fibrillatory-wave amplitude on a standard surface electrocardiogram were obtained during AF before ablation. Results: Low-voltage areas (LVA; 15 cm2 [IQR 8–31]) were detected in 56% of patients. Twenty nine percent of them presented mild, 43% moderate and 28% severe global LVA burden. In univariate analysis, age ≥ 57 years old, female sex, body surface area ≤ 1.76 m2, valvular heart disease, moderate mitral regurgitation, chronic coronary syndrome, hypothyroidism, CHA2DS2-VASc score ≥ 3 and ≥ 4 predicted the presence of LVA. In multivariate analysis only female sex, valvular heart disease and CHA2DS2-VASc ≥ 4 remained statistically significant. AF duration, LA size and function and fibrillatory-waves amplitude were neither associated with the prediction of the LVA, nor severe LVA burden. Conclusions: A LSPAF diagnosis does not indicate the presence of voltage defined fibrosis in many cases. Simple non-invasive screening of the LSPAF population could predict LVA prevalence

Global Effects of Catecholamines on Actinobacillus pleuropneumoniae Gene Expression

Bacteria can use mammalian hormones to modulate pathogenic processes that play essential roles in disease development. Actinobacillus pleuropneumoniae is an important porcine respiratory pathogen causing great economic losses in the pig industry globally. Stress is known to contribute to the outcome of A. pleuropneumoniae infection. To test whether A. pleuropneumoniae could respond to stress hormone catecholamines, gene expression profiles after epinephrine (Epi) and norepinephrine (NE) treatment were compared with those from untreated bacteria. The microarray results showed that 158 and 105 genes were differentially expressed in the presence of Epi and NE, respectively. These genes were assigned to various functional categories including many virulence factors. Only 18 genes were regulated by both hormones. These genes included apxIA (the ApxI toxin structural gene), pgaB (involved in biofilm formation), APL_0443 (an autotransporter adhesin) and genes encoding potential hormone receptors such as tyrP2, the ygiY-ygiX (qseC-qseB) operon and narQ-narP (involved in nitrate metabolism). Further investigations demonstrated that cytotoxic activity was enhanced by Epi but repressed by NE in accordance with apxIA gene expression changes. Biofilm formation was not affected by either of the two hormones despite pgaB expression being affected. Adhesion to host cells was induced by NE but not by Epi, suggesting that the hormones affect other putative adhesins in addition to APL_0443. This study revealed that A. pleuropneumoniae gene expression, including those encoding virulence factors, was altered in response to both catecholamines. The differential regulation of A. pleuropneumoniae gene expression by the two hormones suggests that this pathogen may have multiple responsive systems for the two catecholamines