Flecainide is a safe and effective treatment for pre-excited atrial fibrillation rapidly conducted to the ventricle in pregnant women: a case series.

BACKGROUND: Pregnancy is associated with an increased incidence of cardiac arrhythmias likely due to hormonal, haemodynamic, and autonomic changes. Yet, there is little data available regarding the efficacy and safety of anti-arrhythmic agents to prevent pre-excited atrial fibrillation (AF) in pregnant women. CASE SUMMARY: We report on three pregnant women who developed AF rapidly conducted to the ventricle through an overt accessory pathway as the first manifestation of Wolff-Parkinson-White syndrome. DISCUSSION: All patients were treated with flecainide with neither arrhythmias recurrence nor adverse events of the treatment. Mechanisms of action and clinical efficacy of flecainide are discussed.

Selectivity of Terpyridine Platinum Anticancer Drugs for G-quadruplex DNA.

Guanine-rich DNA can form four-stranded structures called G-quadruplexes (G4s) that can regulate many biological processes. Metal complexes have shown high affinity and selectivity toward the quadruplex structure. Here, we report the comparison of a panel of platinum (II) complexes for quadruplex DNA selective recognition by exploring the aromatic core around terpyridine derivatives. Their affinity and selectivity towards G4 structures of various topologies have been evaluated by FRET-melting (Fluorescence Resonance Energy Transfert-melting) and Fluorescent Intercalator Displacement (FID) assays, the latter performed by using three different fluorescent probes (Thiazole Orange (TO), TO-PRO-3, and PhenDV). Their ability to bind covalently to the c-myc G4 structure in vitro and their cytotoxicity potential in two ovarian cancerous cell lines were established. Our results show that the aromatic surface of the metallic ligands governs, in vitro, their affinity, their selectivity for the G4 over the duplex structures, and platination efficiency. However, the structural modifications do not allow significant discrimination among the different G4 topologies. Moreover, all compounds were tested on ovarian cancer cell lines and normal cell lines and were all able to overcome cisplatin resistance highlighting their interest as new anticancer drugs.

Blockade of the renin-angiotensin-aldosterone system in patients with arrhythmogenic right ventricular dysplasia: A double-blind, multicenter, prospective, randomized, genotype-driven study (BRAVE study).

Arrhythmogenic right ventricular dysplasia (ARVD) is a rare cardiomyopathy characterized by the progressive replacement of cardiomyocytes by fatty and fibrous tissue in the right ventricle (RV). These infiltrations lead to cardiac electrical instability and ventricular arrhythmia. Current treatment for ARVD is empirical and essentially based on treatment of arrhythmia. Thus, there is no validated treatment that will prevent the deterioration of RV function in patients with ARVD. The aim of the BRAVE study is to evaluate the effect of ramipril, an angiotensin-converting enzyme inhibitor, on ventricular myocardial remodeling and arrhythmia burden in patients with ARVD. Despite the fact that myocardial fibrosis is one of the structural hallmarks of ARVD, no study has tested an antifibrotic drug in ARVD patients. The trial is a double-blind, parallel, multicenter, prospective, randomized, phase 4 drug study. Patients will be randomized into 2 groups, ramipril or placebo. The 120 patients (60 per group) will be enrolled by 26 centers in France. Patients will be followed up every 6 months for 3 years. The 2 co-primary endpoints are defined as the difference of telediastolic RV volume measured by magnetic resonance imaging between baseline and 3 years of follow-up, and the change in arrhythmia burden during the 3 years of follow-up. A decrease in RV and/or left ventricular deterioration and in arrhythmia burden are expected in ARVD patients treated with ramipril. This reduction will improve quality of life of patients and will reduce the number of hospitalizations and the risk of terminal heart failure.

Interactions of Pt-ttpy with G-Quadruplexes Originating from Promoter Region of the c-myc Gene Deciphered by NMR and Gel Electrophoresis Analysis.

This study provides insights into the interactions of Pt-ttpy, that is, a metallo-organic heterocycle-comprising platinum(II) complex of terpyridine, and G-quadruplexes adopted by G-rich DNA from the transcriptional regulatory element of the c-myc gene, a well-known attractive target for artificial modulation of oncogene expression. A previously noted drug-like potential of Pt-ttpy relies on its antiproliferative activity on cancer cells and its increased selectivity for G-quadruplex binding attributed to the combination of distinct interacting modes. The predominant interaction between the herein used models of a parallel G-quadruplex exhibiting short propeller-type loops and Pt-ttpy occurs through stacking to the outer G-quartets. The presence of adenine versus thymine residue at the 5'-end overhanging region allows the coordinative binding of Pt-ttpy to the G-quadruplex structure. Interestingly, Pt-ttpy triggers the formation of the G-quadruplex even in the absence of cations. Furthermore, NMR-based characterisation revealed common structural features of Pt-ttpy-G-quadruplex complexes in the presence and absence of cations, which indicate that cations may be expelled from the cores of the corresponding structures.

Increased intracardiac vascular endothelial growth factor levels in patients with paroxysmal, but not persistent atrial fibrillation.

AIMS: Although inflammation appears to play a pivotal role in the pathophysiology of atrial fibrillation (AF), the source of inflammation is unknown. We hypothesized that multilevel measurement of several inflammatory proteins in AF patients would help assess the extent and the source of inflammation. METHODS AND RESULTS: Thirty-nine patients with paroxysmal AF, 33 with persistent AF, and 9 control patients with Wolff-Parkinson-White syndrome were enrolled. Peripheral, left atrial, coronary sinus, and pulmonary vein blood samples were obtained during catheterization. Serum levels of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), soluble intercellular adhesion molecule 1 (sICAM-1), and transforming growth factor-ß1 (TGF-ß1) were measured at the four sampled sites. Interleukin-8, sICAM-1, and TGF-ß1 levels did not differ among groups at any of the sampled sites. Peripheral VEGF levels were higher in both paroxysmal and persistent AF patients than in controls (P ≤ 0.03). Left atrial VEGF levels were higher in paroxysmal AF (P = 0.05), but not in persistent AF (P = 0.32), compared with controls. Coronary sinus and pulmonary vein VEGF levels did not differ significantly among groups. CONCLUSIONS: Low levels of several inflammatory markers in both paroxysmal and persistent AF patients suggest that the inflammatory process is of low grade, if present. In the context of normal pulmonary vein VEGF levels, the heart itself is the most likely source of high left atrial VEGF levels in paroxysmal AF patients; however, this disorder appears to be a transient event in the natural history of AF.