Vagal Paroxysmal Atrial Fibrillation: Prevalence and Ablation Outcome in Patients Without Structural Heart Disease

Prevalence of Vagal Paroxysmal Atrial Fibrillation . Introduction: The prevalence of vagal and adrenergic atrial fibrillation (AF) and the success rate of pulmonary vein isolation (PVI) are not well defined. We investigated the prevalence of vagal and adrenergic AF and the ablation success rate of antral pulmonary vein isolation (APVI) in patients with these triggers compared with patients with random AF. Methods and Results: Two hundred and nine consecutive patients underwent APVI due to symptomatic drug refractory paroxysmal AF. Patients were diagnosed as vagal or adrenergic AF if >90% of AF episodes were related to vagal or adrenergic triggers; otherwise, a diagnosis of random AF was made. Clinical, electrocardiogram (ECG), and Holter follow‐up was every 3 months in the first year and every 6 months afterward and for symptoms. Of 209 patients, 57 (27%) had vagal AF, 14 (7%) adrenergic AF, and 138 (66%) random AF. Vagal triggers were sleep (96.4%), postprandial (96.4%), late post‐exercise (51%), cold stimulus (20%), coughing (7%), and swallowing (2%). At APVI, 94.3% of patients had isolation of all veins. Twenty‐five (12%) patients had a second APVI. At a follow‐up of 21 ± 15 months, the percentage of patients free of AF was 75% in the vagal group, 86% in the adrenergic group, and 82% for random AF (P = 0.51). Conclusion: In patients with PAF and no structural heart disease referred for APVI, vagal AF is present in approximately one quarter. APVI is equally effective in patients with vagal AF as in adrenergic and random AF. (J Cardiovasc Electrophysiol, Vol. 21, pp. 489‐493, May 2010)     

A New Variant of Hereditary Hemolytic Anemia With Stomatocytosis and Erythrocyte Cation Abnormality

A new variant of congenital hemolyticanemia associated with stomatocytosis,reticulocytosis, decreased osmotic fragility, type I autohemolysis and shortened erythrocyte survival without specific splenic sequestration was discoveredin three siblings of Swiss-German ancestry. Increased intracellular sodium(two to three times normal) and slightlydecreased intracellular potassium weredetected. Total sodium efflux was eight-fold greater than normal but total potassium influx was normal and ouabain-sensitive potassium influx was decreased.The ouabain-sensitive sodium efflux:potassium influx ratio was 26:1 ratherthan the 3:2 ratio noted in normal cells.The consanguineous parents, four othersiblings, and 44 other family membershad mild stomatocytosis, reticulocytosis,and, when studied, decreased osmoticfragility, increased autohemolysis, intermediate abnormalities of cation content,cation flux, and moderate shortening oferythrocyte survival. Autosomal dominant inheritance was suggested. Noabnormalities of RBC enzymes, hemoglobin or lipids were observed. No abnormalities of membrane protein weredetected on acrylamide gel. Substratedepletion of these hypermetabolic cellsresulted in intracellular dehydrationwith potassium loss in excess of sodiumgain and decreased deformability. Although the exact nature of the defectresponsible for hemolysis is unknown,this syndrome differs from other hereditary hemolytic anemias associated withstomatocytosis.

Submitted on December 21, 1970 Revised on March 16, 1971 Accepted on March 29, 1971     

Genotype does not predict severity of behavioural phenotype in juvenile neuronal ceroid lipofuscinosis (Batten disease)

Aim The primary aim of this investigation was to examine genotype and clinical phenotype differences in individuals with juvenile neuronal ceroid lipofuscinosis (JNCL) who were homozygous for a common disease‐causing deletion or compound heterozygous. The secondary aim was to cross‐validate the Child Behavior Checklist (CBCL) and the Unified Batten Disease Rating Scale (UBDRS), a disease‐specific JNCL rating scale. Method Sixty individuals (28 males, 32 females; mean age 15y 1mo, SD 4y 9mo, range 5y 8mo–31y 1mo) with JNCL completed the UBDRS. Results No significant genotype and clinical phenotype differences were identified when comparing individuals homozygous for the deletion with a heterogeneous group of compound heterozygous individuals. There were significant correlations among related behaviour items and scales on the CBCL and UBDRS (Spearman’s rho ranging from 0.39 [p<0.05] to 0.72 [p<0.01]). Behaviour and physical function ratings were uncorrelated, supporting divergent validity of these two constructs in JNCL. Interpretation Previous reports of genotype and clinical phenotype differences were unsupported in this investigation, which did not find differences between individuals homozygous or heterozygous for the CLN3 deletion. The CBCL, an already validated measure of behaviour problems, appears valid for use in JNCL and cross‐validates well with the UBDRS.     

Early nephron formation in the developing mouse kidney

This paper reports 3-dimensional confocal microscopy observations on how nephrogenic aggregates form from the NCAM- and Pax2-positive caps (4–5 cells deep) of condensed metanephric mesenchyme surrounding the duct tips of the mouse kidney. Aggregates of 6–8 cells are first seen at ∼E12.5–12.75 immediately proximal to this cap, closely abutting the duct surface. As the tip advances, NCAM expression is maintained in the cap but is otherwise restricted to aggregates whose cells rapidly epithelialise, forming tubules that invade the duct epithelium. Pax2 expression studies shows how the rind of nephrogenic blastemal cells forms: as duct tips extend towards the kidney surface, the associated Pax2+ cells form patches of cells on the kidney surface. These observations revise our knowledge of the timing and process of nephron initiation.     

Anticoagulant prophylaxis to prevent asymptomatic deep vein thrombosis in hospitalized medical patients: a systematic review and meta-analysis

Summary.  Background:  The effect of anticoagulant prophylaxis on the prevention of deep vein thrombosis (DVT) should include an investigation of both clinical and subclinical DVT. We conducted a systematic review to determine whether anticoagulant prophylaxis reduces the risk of asymptomatic DVT compared to no prophylaxis in at-risk hospitalized medical patients. Methods:  MEDLINE, EMBASE, and the Cochrane Library were searched through March 2007 for randomized trials of anticoagulant prophylaxis for the prevention of asymptomatic DVT, assessed by venogram or ultrasound. We assessed four outcomes: all asymptomatic DVT, asymptomatic proximal DVT, major bleeding and mortality. Random effects meta-analyses were performed and results were expressed using relative risk (RR) and 95% confidence intervals (95% CIs). Results:  Four trials including 5516 patients were eligible. Our pooled analysis demonstrated that compared to placebo, anticoagulant prophylaxis was associated with a significantly lower risk of any asymptomatic DVT (RR 0.51; 95% CI 0.39–0.67) and asymptomatic proximal DVT (RR 0.45; 95% CI 0.31–0.65). Anticoagulant prophylaxis was associated with a significantly increased risk of major bleeding compared to placebo (RR 2.00; 95% CI 1.05–3.79). There was no significant difference in the pooled estimate for all-cause mortality. Anticoagulant prophylaxis conferred an absolute risk reduction of any DVT and proximal DVT of 2.6% and 1.8%, respectively, and was associated with a 0.5% absolute risk increase in major bleeding. Conclusions:  Anticoagulant prophylaxis is effective in preventing asymptomatic DVT in at-risk hospitalized medical patients but is associated with an increased bleeding risk. The therapeutic benefits of anticoagulant prophylaxis appear to outweigh the risks of bleeding.     

Late Gadolinium Enhancement of the Esophagus is Common on Cardiac MR Several Months after Pulmonary Vein Isolation: Preliminary Observations

Background: Pulmonary vein isolation (PVI) as a treatment for atrial fibrillation (AF) is commonly performed. This procedure can damage the esophagus. Late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR) offers noninvasive assessment of scar. We sought to examine the prevalence of esophageal hyperenhancement on LGE‐CMR prior to and following PVI. Methods: Seventy‐four patients underwent LGE‐CMR prior to and 1.7 ± 1.9 months post PVI for AF. Transmural esophageal hyperenhancement was visually assessed. The pre‐ and post PVI esophageal position was measured, relative to the vertebral body. Results: Prior to PVI, 3% (2/74) of patients had esophageal LGE on CMR. At post‐PVI follow‐up, 30% (23/74) of the studies demonstrated new esophageal hyperenhancement adjacent to an ablation site. Most (74%, 17/27) positive esophageal LGE studies were performed >30 days after PVI, while no (0/9) studies performed >2 months post PVI were positive for esophageal hyperenhancement. The presence of post‐procedural esophageal hyperenhancement was not associated with longer ablation time (P = 0.42), use of an irrigated catheter (74% with LGE vs 47% without, P = 0.16), right‐sided esophageal location (56% with LGE vs 39% without, P = 0.17), size of left atrium cavity (58 ± 8 mm with LGE vs 61 ± 10 mm without, P = 0.15), or the timing of the LGE‐CMR study after PVI (36 ± 10 days with LGE vs 60 ± 66 days without, P = 0.09). Conclusion: Though rare before PVI, new esophageal LGE is seen in almost one‐third of patients after PVI. The clinical implications to remain to be explored, but clinicians should be aware of this frequent imaging finding. (PACE 2010; 33:661–666)     

Utility and Safety of Axillo‐subclavian Venous Imaging with Carbon Dioxide (CO2) Prior to Chronic Lead System Revisions

Background: Prior to attempting placement of one or more electrodes to revise existing rhythm control devices, patency of the central veins should be documented, in view of a high incidence of significant chronic occlusions. Since iodinated contrast venography may be contraindicated in select situations, imaging of the axillo‐subclavian venous system with gaseous carbon dioxide (CO₂) was evaluated prospectively in 23 consecutive individuals who were considered for revision of previously implanted pacemaker or automatic cardioverter defibrillator lead systems. Methods: Approximately 20 mL of CO₂ were manually infused via CO₂ primed injection tubing into a vein at or above the level of the antecubital fossa ipsilateral to the side of prior lead placements. Digital subtraction imaging over the axillo‐subclavian region, lower neck, and mediastinum was performed. Formal interpretation was obtained from one of three interventional radiologists and at least one electrophysiologist. Results: Significant venous occlusions were identified in five (22%) patients. Vascular access utilized for the subsequent 18 revisions performed included the imaged patent ipsilateral vein in 14 patients and the contralateral, right‐sided subclavian venous system in three patients. One patient required epicardial left ventricular lead placement. There were no complications from venography. Conclusions: Axillo‐subclavian venography with gaseous CO₂ in patients undergoing pacemaker or implantable cardioverter defibrillator lead revisions is feasible and safe when use of iodinated dye is contraindicated. This technique should be employed in patients with azotemia, dye contrast allergies, or significant inflammation in the vicinity of the intravenous line insertion. (PACE 2010; 790–794)     

Cell-to-Cell Electrical Interactions During Early and Late Repolarization

Cardiac electrical activity is significantly affected by variations in the conductance of gap junctions that connect myocytes to one another. To better understand how intrinsic (single cell) electrical activity is modulated by junctional conductance, we used a two-myocyte coupling system in which physically separate cells were electrically coupled via a variable resistance set by the investigator. This brief review summarizes our findings regarding: (1) the effect of the early phase of action potential repolarization (phase 1) and transient outward current ( I _to) on action potential conduction, and (2) the effect of coupling on the action potential plateau (late repolarization). We found that inhibition of I _to markedly increased the ability of action potentials to propagate from cell-to-cell when junctional conductance was low. Electrically coupling two myocytes together also suppressed their beat-to-beat variability in action potential duration and contraction. Similarly, early afterdepolarizations (EADS) were readily suppressed by connecting a normal myocyte to one generating EADs. This high sensitivity of the plateau to variations in junctional interactions arises from the large increase in membrane resistance that occurs during this phase of the action potential.