An Approach to Catheter Ablation of Cavotricuspid Isthmus Dependent Atrial Flutter

Much of our understanding of the mechanisms of macro re-entrant atrial tachycardia comes from study of cavotricuspid isthmus (CTI) dependent atrial flutter. In the majority of cases, the diagnosis can be made from simple analysis of the surface ECG. Endocardial mapping during tachycardia allows confirmation of the macro re-entrant circuit within the right atrium while, at the same time, permitting curative catheter ablation targeting the critical isthmus of tissue located between the tricuspid annulus and the inferior vena cava. The procedure is short, safe and by demonstration of an electrophysiological endpoint - bidirectional conduction block across the CTI - is associated with an excellent outcome following ablation. It is now fair to say that catheter ablation should be considered as a first line therapy for patients with documented CTI-dependent atrial flutter

Atrial Fibrillation Begets Atrial Fibrillation in the Pulmonary Veins On the Impact of Atrial Fibrillation on the Electrophysiological Properties of the Pulmonary Veins in Humans

ObjectivesOur purpose was to investigate the impact of short-lasting atrial fibrillation (AF) on the electrophysiological properties of the atria and pulmonary veins (PVs) in patients devoid of AF.BackgroundThe presence of AF is associated with electrical remodeling processes that promote a substrate for arrhythmia maintenance in the atria, which has been termed “AF begets AF.” However, it is unclear whether those electrical alterations also occur in the PVs.MethodsThirty-five patients with a left-sided accessory pathway and without a prior history of AF were included. After successful ablation, the effective refractory periods (ERPs) and conduction times of the right atrium (RA), left atrium (LA), and the PVs were determined. Afterwards, AF was induced and maintained for a period of 15 min. Thereafter, the stimulation protocol was repeated.ResultsAt baseline, the PVs had significantly longer ERPs than the atria. After exposure to AF, the ERPs of both the atria and the PVs decreased significantly. The ERPs of the PVs, however, decreased by a significantly greater extent than the ERPs of the atria (PVs: 248 ± 27 ms vs. 211 ± 40 ms, p < 0.001; LA: 233 ± 23 ms vs. 214 ± 20 ms, p = 0.004; RA: 226 ± 29 ms vs. 188 ± 20 ms; p = 0.003). After AF exposure, the PVs demonstrated a significant conduction slowing whereas the atria did not (PVs: 125 ± 33 ms vs. 159 ± 37 ms, p < 0.001; LA: 129 ± 26 ms vs. 130 ± 24 ms, p = NS; RA: 192 ± 36 ms vs. 196 ± 32 ms, p = NS). Finally, AF was more frequently induced after the presence of AF, particularly by pacing in the PVs (14% vs. 49%, p = 0.001).ConclusionsNew-onset, short-lasting AF creates electrical characteristics similar to those of patients with AF. However, these alterations are pronounced in the PVs compared with the atria, indicating that “AF begets AF in the PVs” (Electrophysiological Properties of the Pulmonary Veins; NCT00530608)

Shortening of Fibrillatory Cycle Length in the Pulmonary Vein During Vagal Excitation

ObjectivesThe goal of the present prospective study is to evaluate the impact of vagal excitation on ongoing atrial fibrillation (AF) during pulmonary vein (PV) isolation.BackgroundThe role of vagal tone in maintenance of AF is controversial in humans.MethodsTwenty-five patients (18 with paroxysmal AF, 7 with chronic AF) were selected by occurrence of vagal excitation during AF (atrioventricular [AV] block: R-R interval >3 s) produced by PV isolation. Fibrillatory cycle length (CL) in the targeted PV and coronary sinus (CS) were determined before, during, and after vagal excitation. The CL was available at PV ostium during vagal excitation in 11 patients.ResultsForty-eight episodes of vagal excitation were observed. During vagal excitation, CL abruptly decreased both in CS and PV (CS, 164 ± 20 ms to 155 ± 23 ms, p < 0.0001; PV, 160 ± 22 ms to 143 ± 28 ms, p < 0.0001), and both returned to the baseline value with resumption of AV conduction. The decrease in PVCL occurred earlier (2.5 ± 1.5 s vs. 4.0 ± 2.6 s, p < 0.01) and was of greater magnitude than that in CSCL (16 ± 16 ms vs. 8 ± 9 ms, p < 0.01). A sequential gradient of CL was observed from PV to PV ostium and CS during vagal excitation (138 ± 29 ms, 149 ± 24 ms, and 159 ± 26 ms, respectively). The decrease in CL was significantly greater in paroxysmal than in chronic AF (CS, 11 ± 9 ms vs. 5 ± 7 ms, p < 0.05; PV, 23 ± 25 ms vs. 8 ± 14 ms, p < 0.05).ConclusionsVagal excitation is associated with shortening of fibrillatory CL. This occurs earlier in PV with a sequential gradient to PV ostium and CS, suggesting that vagal excitation enhances a driving role of PV

Molecular insights into antibiotic resistance - how a binding protein traps albicidin

The worldwide emergence of antibiotic resistance poses a serious threat to human health. A molecular understanding of resistance strategies employed by bacteria is obligatory to generate less-susceptible antibiotics. Albicidin is a highly potent antibacterial compound synthesized by the plant-pathogenic bacterium Xanthomonas albilineans. The drug-binding protein AlbA confers albicidin resistance to Klebsiella oxytoca. Here we show that AlbA binds albicidin with low nanomolar affinity resulting in full inhibition of its antibacterial activity. We report on the crystal structure of the drug-binding domain of AlbA (AlbAS) in complex with albicidin. Both α-helical repeat domains of AlbAS are required to cooperatively clamp albicidin, which is unusual for drug-binding proteins of the MerR family. Structure-guided NMR binding studies employing synthetic albicidin derivatives give valuable information about ligand promiscuity of AlbAS. Our findings thus expand the general understanding of antibiotic resistance mechanisms and support current drug-design efforts directed at more effective albicidin analogs

A roadmap to improve the quality of atrial fibrillation management:proceedings from the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference

At least 30 million people worldwide carry a diagnosis of atrial fibrillation (AF), and many more suffer from undiagnosed, subclinical, or 'silent' AF. Atrial fibrillation-related cardiovascular mortality and morbidity, including cardiovascular deaths, heart failure, stroke, and hospitalizations, remain unacceptably high, even when evidence-based therapies such as anticoagulation and rate control are used. Furthermore, it is still necessary to define how best to prevent AF, largely due to a lack of clinical measures that would allow identification of treatable causes of AF in any given patient. Hence, there are important unmet clinical and research needs in the evaluation and management of AF patients. The ensuing needs and opportunities for improving the quality of AF care were discussed during the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference in Nice, France, on 22 and 23 January 2015. Here, we report the outcome of this conference, with a focus on (i) learning from our 'neighbours' to improve AF care, (ii) patient-centred approaches to AF management, (iii) structured care of AF patients, (iv) improving the quality of AF treatment, and (v) personalization of AF management. This report ends with a list of priorities for research in AF patients