Early Ablation Research Articles

Renal Nerve Ablation for Resistant Hypertension

Sympathetic renal denervation, or renal nerve ablation (RNA), has become the new buzz word in hypertension and interventional cardiology. Recent advances in catheter-based approaches have allowed sympathetic fiber interruption through transvascular techniques that are minimally invasive and can be delivered expeditiously and safely. Radiofrequency (RF) energy sources are currently the preferred modalities, but other sources of energy, such as cryoablation, microwave, high-intensity focus ultrasound, and local neurotoxic agent infusion, are under intense investigation. Results thus far have been encouraging and offer promise for the future. The role of the sympathetic nervous system (SNS) in the development of resistant hypertension and cardiovascular disease has long been known, and a great deal of work has been done through the years trying to explore potential interventions to interrupt the sympathetic influence on systemic vasculature and target organs. In this article we attempt an overview of time-dependent interventions on the SNS and examine approaches used in humans and in the many experimental models that offer a better understanding of the role of sympathetic activity in cardiovascular disease. Naturally we focus on methods and techniques addressing sympathetic renal denervation in patients with drug-resistant hypertension, examine the current state of the art, and attempt a look into the future. In 1889, after meticulous experiments on dogs, Bradford1 reported that stimulation of dorsal and splanchnic nerves causes changes in blood pressure (BP) and kidney size measured by plethysmography. Whether BP increased or decreased depended on the anatomic area stimulated, as well as the electric impulse frequency, but outcomes were consistent and reproducible. Neurosurgical treatment of hypertension was independently suggested by researchers in 1923.2 Adson, however, was the first to performed surgical sympathectomy for the treatment of malignant hypertension in 1925.3 During the following years and in the 1930s, Peet in Ann Arbor, Page and …

Mitrofanoff for Valve Bladder Syndrome: Effect on Urinary Tract and Renal Function

Despite early diagnosis and valve ablation, progressive renal impairment develops in a significant proportion of boys born with posterior urethral valves. Bladder dysfunction is thought to have an important role in the etiology of this renal deterioration. We report the outcome of treating bladder dysfunction with clean intermittent catheterization and overnight drainage via a Mitrofanoff appendicovesicostomy with respect to upper tract imaging, urodynamic findings and renal function. All patients were established on a clean intermittent catheterization program via the Mitrofanoff stoma, including 3 or 4 daytime catheterizations and overnight drainage with an indwelling catheter. We analyzed trends in serum creatinine, renal ultrasound appearance and urodynamic data. Mitrofanoff formation was performed in 24 patients with valve bladder syndrome. Median followup was 6.2 years. Hydronephrosis, quantified by combined anteroposterior diameter measurements of the renal pelvis, significantly improved with a mean combined anteroposterior diameter reduction of 14.2 mm (95% CI 7.6-20.9, p ≤ 0.001). Overall bladder dysfunction improved. Capacity was decreased in 9 of 12 patients (75%) initially compared with 12 of 21 (57%) after Mitrofanoff surgery (p = 0.457). Compliance was poor in 75% of patients initially vs 28.6% at followup (p = 0.014). Despite improvements in hydronephrosis and urodynamic parameters the mean estimated glomerular filtration rate deteriorated. End stage renal failure developed in 35% of cases during followup. Treatment of valve bladder with clean intermittent catheterization and overnight drainage via a Mitrofanoff stoma can achieve significant improvements in hydronephrosis and bladder dysfunction urodynamic parameters. However, it does not prevent renal deterioration.

Identifying MRI markers to evaluate early treatment related changes post laser ablation for cancer pain management.

Laser interstitial thermal therapy (LITT) has recently emerged as a new treatment modality for cancer pain management that targets the cingulum (pain center in the brain), and has shown promise over radio-frequency (RF) based ablation which is reported to provide temporary relief. One of the major advantages enjoyed by LITT is its compatibility with magnetic resonance imaging (MRI), allowing for high resolution in vivo imaging to be used in LITT procedures. Since laser ablation for pain management is currently exploratory and is only performed at a few centers worldwide, its short-, and long-term effects on the cingulum are currently unknown. Traditionally treatment effects are evaluated by monitoring changes in volume of the ablation zone post-treatment. However, this is sub-optimal since it involves evaluating a single global parameter (volume) to detect changes pre-, and post-MRI. Additionally, the qualitative observations of LITT-related changes on multi-parametric MRI (MP-MRI) do not specifically address differentiation between the appearance of treatment related changes (edema, necrosis) from recurrence of the disease (pain recurrence). In this work, we explore the utility of computer extracted texture descriptors on MP-MRI to capture early treatment related changes on a per-voxel basis by extracting quantitative relationships that may allow for an in-depth understanding of tissue response to LITT on MRI, subtle changes that may not be appreciable on original MR intensities. The second objective of this work is to investigate the efficacy of different MRI protocols in accurately capturing treatment related changes within and outside the ablation zone post-LITT. A retrospective cohort of studies comprising pre- and 24-hour post-LITT 3 Tesla T1-weighted (T1w), T2w, T2-GRE, and T2-FLAIR acquisitions was considered. Our scheme involved (1) inter-protocol as well as inter-acquisition affine registration of pre- and post-LITT MRI, (2) quantitation of MRI parameters by correcting for intensity drift in order to examine tissue-specific response, and (3) quantification of MRI maps via texture and intensity features to evaluate changes in MR markers pre- and post-LITT. A total of 78 texture features comprising of non-steerable and steerable gradient and second order statistical features were extracted from pre- and post-LITT MP-MRI on a per-voxel basis. Quantitative, voxel-wise comparison of the changes in MRI texture features between pre-, and post-LITT MRI indicate that (a) steerable and non-steerable gradient texture features were highly sensitive as well as specific in predicting subtle micro-architectural changes within and around the ablation zone pre- and post-LITT, (b) FLAIR was identified as the most sensitive MRI protocol in identifying early treatment changes yielding a normalized percentage change of 360% within the ablation zone relative to its pre-LITT value, and (c) GRE was identified as the most sensitive MRI protocol in quantifying changes outside the ablation zone post-LITT. Our preliminary results thus indicate great potential for non-invasive computerized MRI features in determining localized micro-architectural focal treatment related changes post-LITT.

Hydrodynamic modeling of femtosecond laser ablation of metals in vacuum and in liquid

We numerically examine the mechanisms involved in nanoparticle formation by laser ablation of metallic targets in vacuum and in liquid. We consider the very early ablation stage providing initial conditions for much longer plume expansion processes. In the case of ultrashort laser ablation, the initial population of primary nanoparticles is formed at this stage. When a liquid is present, the dynamics of the laser plume expansion differs from that in vacuum. Low compressibility of the ambient liquid results in strong confinement conditions. As a result, ablation threshold rises drastically, the ablated material is compressed, part of it becomes supersaturated and the backscattered material additionally heats the target. The extension of a molten layer leads to the additional ablation at a later stage also favoring nanoparticle formation. The obtained results thus explain recent experimental findings and help to predict the role of the experimental parameters. The performed analysis indicates ways of a control over nanoparticle synthesis.

Optimising Treatment Parameters for Radiofrequency Induced Thermal Therapy (RFiTT): A Comparison of the Manufacturer's Treatment Guidance with a Locally Developed Treatment Protocol

Radiofrequency induced Thermal Therapy (RFiTT) is an established endovenous device for the treatment of varicose veins. Our aim was to compare the manufacturer's treatment guidance with a locally developed treatment protocol on early truncal ablation rates between two patient cohorts. The study was a retrospective analysis of prospectively collected data from 534 patients treated for incompetent truncal saphenous veins between June 2009 and December 2012. Patients were treated either according to the manufacturer's guidance (Treatment 1), a single pullback rate of ≥1.5 s/cm, or according to local protocol (Treatment 2), repeated vein treatment to visibly occlude the vein lumen. Follow-up at 6 weeks and 12 months included duplex examination, assessment of complications, and pain scores for the first postoperative week. 14 patients did not attend follow-up, leaving 98 patients (142 saphenous trunk treatments) who received Treatment 1 and 422 patients (566 saphenous trunk treatments) who received Treatment 2. The two groups were well matched for age, sex, and preoperative vein parameters. Six week occlusion rates were significantly different, with more treatment failures after Treatment 1 (Treatment 1 5.6% vs. Treatment 2 0.9%; p = .0001). Treatment 1 was more likely to produce incomplete ablation (3.5% vs. 0.9%) and non-ablation (2.1% vs. 0.0%) compared with Treatment 2. No major complications occurred in either group and functional outcomes were otherwise comparable between the two treatment methods. Longer-term follow-up at 12 months in the first 100 patients undergoing Treatment 2 demonstrated maintenance of the early advantage, with partial recanalisations in 9% and 2% for Treatments 1 and 2, respectively. Six weeks after treatment with RFiTT, a protocol of repeated vein treatments to visibly obliterate the vein lumen produced more reliable venous occlusion compared with manufacturer's guidance. This advantage is maintained at 12 months.

Altered Macrophage Phenotype Transition Impairs Skeletal Muscle Regeneration

Monocyte/macrophage polarization in skeletal muscle regeneration is ill defined. We used CD11b-diphtheria toxin receptor transgenic mice to transiently deplete monocytes/macrophages at multiple stages before and after muscle injury induced by cardiotoxin. Fat accumulation within regenerated muscle was maximal when ablation occurred at the same time as cardiotoxin-induced injury. Early ablation (day 1 after cardiotoxin) resulted in the smallest regenerated myofiber size together with increased residual necrotic myofibers and fat accumulation. However, muscle regeneration after late (day 4) ablation was similar to controls. Levels of inflammatory cells in injured muscle following early ablation and associated with impaired muscle regeneration were determined by flow cytometry. Delayed, but exaggerated, monocyte [CD11b(+)(CD90/B220/CD49b/NK1.1/Ly6G)(-)(F4/80/I-Ab/CD11c)(-)Ly6C(+/-)] accumulation occurred; interestingly, Ly6C(+) and Ly6C(-) monocytes were present concurrently in ablated animals and control mice. In addition to monocytes, proinflammatory, Ly6C(+) macrophage accumulation following early ablation was delayed compared to controls. In both groups, CD11b(+)F4/80(+) cells exhibited minimal expression of the M2 markers CD206 and CD301. Nevertheless, early ablation delayed and decreased the transient accumulation of CD11b(+)F4/80(+)Ly6C(-)CD301(-) macrophages; in control animals, the later tissue accumulation of these cells appeared to correspond to that of anti-inflammatory macrophages, determined by cytokine production and arginase activity. In summary, impairments in muscle regeneration were associated with exaggerated monocyte recruitment and reduced Ly6C(-) macrophages; the switch of macrophage/monocyte subsets is critical to muscle regeneration.

Focal amplification of the androgen receptor gene in hormone-naive human prostate cancer

Background:Androgen receptor (AR)-gene amplification, found in 20–30% of castration-resistant prostate cancer (CRPCa) is proposed to develop as a consequence of hormone-deprivation therapy and be a prime cause of treatment failure. Here we investigate AR-gene amplification in cancers before hormone deprivation therapy.Methods:A tissue microarray (TMA) series of 596 hormone-naive prostate cancers (HNPCas) was screened for chromosome X and AR-gene locus-specific copy number alterations using four-colour fluorescence in situ hybridisation.Results:Both high level gain in chromosome X (⩾4 fold; n=4, 0.7%) and locus-specific amplification of the AR-gene (n=6, 1%) were detected at low frequencies in HNPCa TMAs. Fluorescence in situ hybridisation mapping whole sections taken from the original HNPCa specimen blocks demonstrated that AR-gene amplifications exist in small foci of cells (⩽600 nm, ⩽1% of tumour volume). Patients with AR gene-locus-specific copy number gains had poorer prostate cancer-specific survival.Conclusion:Small clonal foci of cancer containing high level gain of the androgen receptor (AR)-gene develop before hormone deprivation therapy. Their small size makes detection by TMA inefficient and suggests a higher prevalence than that reported herein. It is hypothesised that a large proportion of AR-amplified CRPCa could pre-date hormone deprivation therapy and that these patients would potentially benefit from early total androgen ablation.

Ventricular arrhythmias in patients of atrial fibrillation treated with flecainide: A case report

Purpose: Flecainide is a class 1C antiarrhythmic drug, especially used for the management of supraventricular arrhythmia. Flecainide also has a recognized proarrhythmic effect in all age groups of adult patients treated for ventricular tachycardia. It is used to treat a variety of cardiac arrhythmias including paroxysmal fibrillation, Paroxysmal Supraventricular tachycardia and ventricular tachycardia. Flecainide works by regulating the flow of sodium in the heart, causing prolongation of the cardiac action potential. The proarrhythmic effects however noted are not widely reported. Case report: We report a case of paroxysmal atrial fibrillation with structurally normal heart who was treated with oral Flecainide. Despite subjective improvement and no adverse events [QTc prolongation] a repeat holter detected him to have multiple short non sustained ventricular arrhythmias. Results: Development of ventricular arrhythmias, salvos &non sustained ventricular tachycardia after a month of initiation of oral Flecainide detected by 24 hours ECG holter lead to discontinuation of Flecainide and subsequent early electro physiological studies and successful ablation. Conclusion: Initiation of oral Flecainide in a case of atrial fibrillation with subjective improvement and regular ECG monitoring, no QTc prolongation can still lead to development of dangerous ventricular arrhythmias. A cautious approach and thorough investigations and follow up are recommended.

Early Radiofrequency Ablation for Twin Reversed Arterial Perfusion TRAP) Sequence: Case Report and Literature Review

Background: High output cardiac failure resulting in fetal death or severe prematurity is a common complication of twin reversed arterial perfusion (TRAP) sequence. Various minimally invasive prenatal interventions have been proposed to improve outcomes for the pump fetus. Uncertainty still exists regarding the optimal timing of these interventions. Early intervention may protect the pump twin against prematurity from complications of cardiac failure or unexpected fetal death, although it carries a risk of procedure related pregnancy loss. Expectant management with surveillance and performing an intervention later in gestation if necessary’ would potentially avoid some procedures but does not protect against unexpected fetal death. Case: A healthy 30 year-old woman, gravida 2 para 1, was diagnosed with TRAP sequence at 13+1 weeks gestation. An uncomplicated ultrasound guided Radiofrequency Ablation (RFA) procedure ablating the vessels in the parasitic mass was performed at 15+0 weeks. The remainder of the pregnancy was uneventful and resulted in a term vaginal delivery of a healthy infant. Conclusion: Based on our current knowledge of TRAP sequence and current instrumentation for fetal surgery, early occlusion of the vessels perfusing an acardiac fetus appears feasible and safe. Randomized trials on timing of intervention are urgently needed.

Flecainide Induced Ventricular Arrhythmias in Atrial Fibrillation

Purpose: Flecainide is a class 1C antiarrhythmic drug especially used for the management of supraventricular arrhythmia. Flecainide also has a recognized proarrhythmic effect in patients treated for ventricular tachycardia. It is used to treat a variety of cardiac arrhythmias including paroxysmal fibrillation, Paroxysmal Supraventricular tachycardia and ventricular tachycardia. Flecainide works by regulating the flow of sodium in the heart, causing prolongation of the cardiac action potential. The proarrhythmic effects however noted are not widely reported. Method: We report a case of paroxysmal atrial fibrillation with structurally normal heart who was treated with oral Flecainide. Despite subjective improvement and no adverse events [QTc prolongation] a repeat holter detected him to have multiple short non sustained ventricular arrhythmias. Results: Development of ventricular arrhythmias, salvos & non sustained ventricular tachycardia after a month of initiation of oral Flecainide detected by 24 hours ECG holter lead to discontinuation of Flecainide and subsequent early electro physiological studies and successful ablation. Conclusion: Initiation of oral Flecainide in a case of atrial fibrillation with subjective improvement and regular ECG monitoring, no QTc prolongation can still lead to development of dangerous ventricular arrhythmias. A cautious approach and thorough investigations and follow up are recommended.

Primary Radiofrequency Ablation of Ventricular Tachycardia Early After Myocardial Infarction

Background— Ventricular tachycardia (VT) is a significant complication of myocardial infarction. Radiofrequency ablation for postinfarct VT is reserved for drug refractory VT or VT storms. Our hypothesis is that radiofrequency ablation in the early postinfarct period could abolish or diminish late recurrences of VT. Methods and Results— Myocardial infarct was induced by balloon occlusion of the left anterior descending artery in 35 sheep. The 25 survivors underwent programmed ventricular stimulation and electroanatomical mapping 8 days postinfarct. Animals with inducible VT (12 out of 25 animals) underwent immediate radiofrequency ablation. Further VT inductions were performed 100 and 200 days postinfarct. At day 8, 3.0±0.9 VT morphologies per animal were inducible. All were successfully ablated with 24±6 applications of radiofrequency energy. All had ablations on the left ventricular endocardium, and 67% had ablations on the right ventricular aspect of the interventricular septum. All targeted arrhythmias were successfully ablated acutely. One animal was euthanized because of hypotension from a serious pericardial effusion. The other 11 survived and remained arrhythmia free on subsequent inductions on the 100th and 200th days ( P <0.001). The 13 animals without inducible VT remained noninducible at the subsequent studies. A historical control arm of 9 animals with inducible VT at day 8 remained inducible at day 100. Conclusions— Radiofrequency ablation on the eighth day after infarction abolished inducibility of VT at late induction studies ≤200 days in an ovine model. Early identification and ablation of VT after infarction may prevent or reduce late ventricular arrhythmias but needs to be validated in clinical studies.

Carotid Chemoreceptor Ablation Improves Survival in Heart Failure: Rescuing Autonomic Control of Cardiorespiratory Function

This study sought to investigate whether selective ablation of the carotid body (CB) chemoreceptors improves cardiorespiratory control and survival during heart failure. Chronic heart failure (CHF) is a recognized health problem worldwide, and novel treatments are needed to better improve life quality and decrease mortality. Enhanced carotid chemoreflex drive from the CB is thought to contribute significantly to autonomic dysfunction, abnormal breathing patterns, and increased mortality in heart failure. Chronic heart failure was induced by coronary ligation in rats. Selective CB denervation was performed to remove carotid chemoreflex drive in the CHF state (16 weeks post-myocardial infarction). Indexes of autonomic and respiratory function were assessed in CB intact and CB denervated animals. CB denervation at 2 weeks post-myocardial infarction was performed to evaluate whether early targeted CB ablation decreases the progression of left ventricular dysfunction, cardiac remodeling, and arrhythmic episodes and improves survival. The CHF rats developed increased CB chemoreflex drive and chronic central pre-sympathetic neuronal activation, increased indexes of elevated sympathetic outflow, increased breathing variability and apnea incidence, and desensitization of the baroreflex. Selective CB ablation reduced the central pre-sympathetic neuronal activation by 40%, normalized indexes of sympathetic outflow and baroreflex sensitivity, and reduced the incidence of apneas in CHF animals from 16.8 ± 1.8 events/h to 8.0 ± 1.4 events/h. Remarkably, when CB ablation was performed early, cardiac remodeling, deterioration of left ventricle ejection fraction, and cardiac arrhythmias were reduced. Most importantly, the rats that underwent early CB ablation exhibited an 85% survival rate compared with 45% survival in CHF rats without the intervention. Carotid chemoreceptors play a seminal role in the pathogenesis of heart failure, and their targeted ablation might be of therapeutic value to reduce cardiorespiratory dysfunction and improve survival during CHF.

Abstract 24: Tubular Vegfa is Required for Renal Microvasculature and Oxygen Sensing

Adequate renal oxygenation is pivotal for maintaining essential functions of the kidney. Vascular endothelial growth factor A (VEGFA) plays a key role in vascular formation and maintenance, processes that are critical for sufficient tissue perfusion and oxygenation. Here we show that Vegfa is expressed in select tubular epithelial cells within the nephron, while expression of its receptor ( Kdr/Vegfr2 ) is restricted largely to capillary beds. Early genetic ablation of tubular Vegfa allows the formation of a grossly normal kidney. However, microvascular density is markedly reduced, leading to increased renal hypoxia. As a consequence the mice develop pronounced polycythemia (81 ± 1.62 vs. 58 ± 0.87 % Hematocrit), due to an increase in serum erythropoietin concentration (426.5 ± 49.3 vs. 249.3 ± 13.6 pg/ml). The elevation in circulating erythropoietin is elicited by an augmented renal production of the hormone, and occurs independent of changes in hepatic expression. In kidney, expression of classical hypoxia-inducible factor-1 responsive transcripts remains unaltered; suggesting that erythropoiesis partly compensates the capillary rarefaction. An increase in diastolic blood pressure (DBP, 112 ± 3.7 vs. 104 ± 1.6 mmHg) is present in mice lacking tubular Vegfa maintained on a normal diet, while systolic blood pressure (SBP, 139 ± 2.8 vs. 135 ± 2.8 mmHg) does not change. The difference in diastolic pressure is ablated when dietary NaCl content changed (DBP: 107 ± 3.1 vs. 103 ± 2.7 mmHg; SBP: 132 ± 4.1 vs. 131 ± 2.9 mmHg; for low NaCl), or when angiotensin II is infused (DBP: 137 ± 6.7 vs. 134 ± 3.8 mmHg; SBP: 161 ± 7.6 vs. 162 ± 9.3 mmHg). Moreover, renal electrolyte excretion remains unperturbed by reductions in tubular Vegfa. In conclusion, tubular Vegfa is critical for adequate development of renal microvasuculature, a prerequisite for proper oxygenation of the kidney. Compensatory polycythemia likely prevents severe perturbations of renal function in this model. In addition, increased diastolic blood pressure may occur as a consequence of capillary rarefaction within the kidney.

Early anther ablation triggers parthenocarpic fruit development in tomato

Fruit set and fruit development in tomato is largely affected by changes in environmental conditions, therefore autonomous fruit set independent of fertilization is a highly desirable trait in tomato. Here, we report the production and characterization of male-sterile transgenic plants that produce parthenocarpic fruits in two tomato cultivars (Micro-Tom and Moneymaker). We generated male-sterility using the cytotoxic gene barnase targeted to the anthers with the PsEND1 anther-specific promoter. The ovaries of these plants grew in the absence of fertilization producing seedless, parthenocarpic fruits. Early anther ablation is essential to trigger the developing of the transgenic ovaries into fruits, in the absence of the signals usually generated during pollination and fertilization. Ovaries are fully functional and can be manually pollinated to obtain seeds. The transgenic plants obtained in the commercial cultivar Moneymaker show that the parthenocarpic development of the fruit does not have negative consequences in fruit quality. Throughout metabolomic analyses of the tomato fruits, we have identified two elite lines which showed increased levels of several health promoting metabolites and volatile compounds. Thus, early anther ablation can be considered a useful tool to promote fruit set and to obtain seedless and good quality fruits in tomato plants. These plants are also useful parental lines to be used in hybrid breeding approaches.

Current practice in Europe: how do we manage patients with ventricular tachycardia? European Heart Rhythm Association survey

The purpose of the EP wire is to examine the clinical practice in the management of sustained ventricular tachycardia (VT), with special focus on diagnostic and therapeutic strategies. Forty-five European centres, all members of the EHRA-EP Research network completed the questions of the survey. There was an equal distribution of centres with high, medium, and low volume of activity. The most common aetiologies were: post-myocardial infarction ischaemic heart disease (55%), followed by idiopathic dilated cardiomyopathy (18%), and idiopathic VT (11%) and others (12%). Cardiac magnetic resonance imaging was performed in more than 50% of patients in 24 centres (62.2%). Invasive electrophysiological study was performed in more than 70% of patients in 16 centres (35.6%), between 51 and 70% in 9 (20%), below 50% in 20 (44.5%). In 39 centres (86.7%), implantable cardioverter defibrillator implantation was considered in all patients with structural heart disease and left ventricular ejection fraction <35%. In the setting of secondary prevention, early radiofrequency ablation of the VT was performed in more than 50% of the patients in only five centres (11.4%). Sequential endo-epicardial approach was reported in 52.2% of centres.

Atrial fibrillation in endurance athletes

There is a growing population of veteran endurance athletes, regularly participating in training and competition. Although the graded benefit of exercise on cardiovascular health and mortality is well established, recent studies have raised concern that prolonged and strenuous endurance exercise may predispose to atrial and ventricular arrhythmias. Atrial fibrillation (AF) and atrial flutter are facilitated by atrial remodelling, atrial ectopy, and an imbalance of the autonomic nervous system. Endurance sports practice has an impact on all of these factors and may therefore act as a promoter of these arrhythmias. In an animal model, long-term intensive exercise training induced fibrosis in both atria and increased susceptibility to AF. While the prevalence of AF is low in young competitive athletes, it increases substantially in the aging athlete, which is possibly associated with an accumulation of lifetime training hours and participation in competitions. A recent meta-analysis revealed a 5-fold increased risk of AF in middle-aged endurance athletes with a striking male predominance. Beside physical activity, height and absolute left atrial size are independent risk factors for lone AF and the stature of men per se may explain part of their higher risk of AF. Furthermore, for a comparable amount of training volume and performance, male non-elite athletes exhibit a higher blood pressure at rest and peak exercise, a more concentric type of left ventricular remodelling, and an altered diastolic function, possibly contributing to a more pronounced atrial remodelling. The sports cardiologist should be aware of the distinctive features of AF in athletes. Therapeutic recommendations should be given in close cooperation with an electrophysiologist. Reduction of training volume is often not desired and drug therapy not well tolerated. An early ablation strategy may be appropriate for some athletes with an impaired physical performance, especially when continuation of competitive activity is intended. This review focuses on the prevalence, risk factors, and mechanisms of AF in endurance athletes, and possible therapeutic options.

A less aggressive therapeutic option for electrical storm.

Electrical storm (ES) describes the rapidly clustering ventricular fibrillation (VF) that requires multiple cardioversions. Emerging evidence suggests that Purkinje arborization and sympathetic nerve regeneration play a major role in initiating malignant arrhythmias. We report the case of two patients who, after having survived an acute myocardial infarction (MI), developed repetitive episodes of polymorphic ventricular tachycardia and VF one week after percutaneous revascularization, triggered by monomorphic premature ventricular contractions (PVCs). Owing to repetitive and drug-refractory VF episodes, temporary atrial overdrive pacing was attempted with complete suppression of VF. In the following month, recurrence of ventricular arrhythmia was inversely related to the atrial pacing rate. Although antiarrhythmic drugs other than beta-blockers had been discontinued, neither PVCs nor ventricular arrhythmias recurred at one-month follow-up when the lower pacing rate was set at 60 bpm. In conclusion in these patients, ES was likely related to nerve sprouting after ischemic injury. This chaotic phenomenon occurs early after tissue damage and shows a peak seven days after acute MI with degeneration of superfluous axon branches. High pacing rates can reduce early after depolarizations and suppress PVCs, thus preventing ES. On these grounds, ES patients may be treated with temporary overdrive pacing rather than early radiofrequency ablation.

Egr2::Cre Mediated Conditional Ablation of Dicer Disrupts Histogenesis of Mammalian Central Auditory Nuclei

Histogenesis of the auditory system requires extensive molecular orchestration. Recently, Dicer1, an essential gene for generation of microRNAs, and miR-96 were shown to be important for development of the peripheral auditory system. Here, we investigated their role for the formation of the auditory brainstem. Egr2::Cre-mediated early embryonic ablation of Dicer1 caused severe disruption of auditory brainstem structures. In adult animals, the volume of the cochlear nucleus complex (CNC) was reduced by 73.5%. This decrease is in part attributed to the lack of the microneuronal shell. In contrast, fusiform cells, which similar to the granular cells of the microneural shell are derived from Egr2 positive cells, were still present. The volume reduction of the CNC was already present at birth (67.2% decrease). The superior olivary complex was also drastically affected in these mice. Nissl staining as well as Vglut1 and Calbindin 1 immunolabeling revealed that principal SOC nuclei such as the medial nucleus of the trapezoid body and the lateral superior olive were absent. Only choline acetyltransferase positive neurons of the olivocochlear bundle were observed as a densely packed cell group in the ventrolateral area of the SOC. Mid-embryonic ablation of Dicer1 in the ventral cochlear nucleus by Atoh7::Cre-mediated recombination resulted in normal formation of the cochlear nucleus complex, indicating an early embryonic requirement of Dicer1. Quantitative RT-PCR analysis of miR-96 demonstrated low expression in the embryonic brainstem and up-regulation thereafter, suggesting that other microRNAs are required for proper histogenesis of the auditory brainstem. Together our data identify a critical role of Dicer activity during embryonic development of the auditory brainstem.

Striking Similarities in Fly and Vertebrate Olfactory Network Formation

​OlfactionOlfaction is a primitive sensory ability that is common to vertebrates and insects, but the neural circuits that underlie the ability to smell are very complex. Before an odor is recognized, it has to be processed through several stages by neurons in the olfactory system. Olfactory sensory neurons (OSNs), which detect odors at the first stage of processing, form precise connections with cells in brain structures called glomeruli, whose specific activation patterns contain information about odor identity. Despite the common design principles in vertebrates and insects, there are important differences. OSNs drive the formation of glomeruli in vertebrates, but cells in glomeruli develop independently of OSNs in adult insects. Olfactory projection neurons (left, red) are absent following early unilateral ablation of presynaptic sensory neurons (right). This week in PLOS Biology, Lucia Prieto-Godino of the University of Cambridge and her collaborators report the results of the first systematic investigation of how the olfactory network assembles in fruit fly embryos. They found that the activity of OSNs is crucial for the proper formation of connections in the olfactory system during these early stages of development. The findings reveal surprising similarities between vertebrates and insect embryos in the formation of olfactory networks. Specifically, they found that projection neurons in the glomeruli of fruit fly embryos only formed extensions that would eventually connect with other neurons after being contacted by OSNs, unlike the pattern seen in adult fruit flies. Projection neurons were more likely to survive when they were contacted by OSNs, and the activity of OSNs controlled the growth of extensions formed by projection neurons. OSN activity also controlled how OSNs formed connections with cells in glomeruli. When the researchers genetically silenced OSN activity, they found that the OSNs formed connections that extended across a broader-than-normal swath of glomeruli, similar to previous findings in vertebrates. This suggests that OSN activity is crucial for the normal wiring of the olfactory network. The study reveals new insights into the development of the olfactory network in insect embryos and shows that OSN activity plays a key role in guiding the development of the olfactory circuitry. Surprisingly, these patterns resemble those observed in vertebrates, but not adult fruit flies. Because neural circuits in other sensory and motor systems share similar properties, the findings may represent general mechanisms that underlie the development of networks in the nervous system. Prieto-Godino LL, Diegelmann S, Bate M (2012) Embryonic Origin of Olfactory Circuitry in Drosophila: Contact and Activity-Mediated Interactions Pattern Connectivity in the Antennal Lobe. doi:10.1371/journal.pbio.1001400

Asymptomatic Wolff-Parkinson-White Syndrome Should be Ablated.

Wolff-Parkinson-White syndrome (WPW) is associated with a small but lifetime risk of cardiac arrest and/or sudden cardiac death (SCD). However, the exact risk is not well defined, particularly in asymptomatic persons. Over recent years the authors have collected and reported new follow-up data among a large number of asymptomatic WPW patients, particularly children, intensively followed. These data have significantly contributed to the knowledge and definition of the natural history of WPW from childhood to adulthood. The risk of SCD is higher in asymptomatic children than in adults, and early ablation can be offered only to selected subjects after electrophysiologic testing.