Despite rescue pLVAD insertion, hemodynamic collapse during VT ablation is associated with a persistently high 30-day mortality. Further studies are warranted to predict hemodynamic collapse and to refine the role of pLVAD in this setting.

Background-Long-QT syndrome (LQTS) is an inherited disorder associated with sudden cardiac death. The cytoskeletal protein syntrophin-␣ 1 (SNTA1) is known to interact with the cardiac sodium channel (hNa v 1.5), and we hypothesized that SNTA1 mutations might cause phenotypic LQTS in patients with genotypically normal hNa v 1.5 by secondarily disturbing sodium channel function. Methods and Results-Mutational analysis of SNTA1 was performed on 39 LQTS patients (QTcՆ480 ms) with previously negative genetic screening for the known LQTS-causing genes. We identified a novel A257G-SNTA1 missense mutation, which affects a highly conserved residue, in 3 unrelated LQTS probands but not in 400 ethnic-matched control alleles. Only 1 of these probands had a preexisting family history of LQTS and sudden death with an additional intronic variant in KCNQ1. Electrophysiological analysis was performed using HEK-293 cells stably expressing hNa v 1.5 and transiently transfected with either wild-type or mutant SNTA1 and, in neonatal rat cardiomyocytes, transiently transfected with either wild-type or mutant SNTA1. In both HEK-293 cells and neonatal rat cardiomyocytes, increased peak sodium currents were noted along with a 10-mV negative shift of the onset and peak of currents of the current-voltage relationships. In addition, A257G-SNTA1 shifted the steady-state activation (V h ) leftward by 9.4 mV, whereas the voltage-dependent inactivation kinetics and the late sodium currents were similar to wild-type SNTA1. Conclusion-SNTA1

BACKGROUND Mutations in the SCN5A gene, which encodes the cardiac sodium channel, have been implicated in the pathogenesis of Brugada syndrome (BrS). Febrile illnesses have been recognized to unmask and/or trigger the BrS phenotype. However, the patho-physiological mechanism has not been fully elucidated. OBJECTIVE A novel SCN5A missense mutation, V1340I, was identified in a patient with BrS suffering from frequent episodes of polymorphic ventricular tachycardia (VT) and syncope associated with fever. The biophysical modifications of hNav1.5 by V1340I were studied. METHODS The effects of the V1340I mutation were studied in the 2 splice variants, SCN5A and SCN5A-Q1077del (delQ), using patch-clamp techniques at various temperatures between 22°C and 40°C. RESULTS At 22°C, V1340I-SCN5A generated markedly diminished sodium currents compared to the wild-type (WT) SCN5A. On the contrary, V1340I-delQ generated almost identical current density compared to the WT-delQ. However, V1340I-delQ significantly attenuated the peak current density compared to the WT-delQ at 32°C, 37°C and 40°C. The voltage dependency of steady-state activation was leftward shifted both in WT-delQ and V1340I-delQ at 40°C. In addition, the V1340I-delQ accelerated the recovery time course from fast inactivation compared to the WT-delQ at 40°C. Immunohistochemical staining showed that both V1340I-SCN5A and V1340I-dQ were expressed in the plasma membrane. CONCLUSION Our study supports the concept that febrile illness predisposes individuals who carry a loss of function SCN5A mutation, such as V1340I, to fever-induced ventricular arrhythmias in BrS by significantly reducing the sodium currents in the hyperthermic state.

The mechanisms leading to formation of spontaneous echo contrast (SEC), a smoke-like echo on echocardiography, are still controversial. To further explore the clinical implications and factors related to SEC formation, the correlation among echocardiographic variables, hematologic parameters or platelet aggregability, and the occurrence of SEC was studied in 119 patients with chronic nonvalvular atrial fibrillation. There were 75 men and 44 women with a mean age of 65 ± 10 years (range 38-88). Left atrial SEC was detected in 39 patients (33%) by transesophageal echocardiography. Patients with history of systemic embolism were more frequently found to have left atrial SEC and left atrial thrombus by univariate analysis. Multivariate analysis showed that left atrial SEC (p < 0.001) was the only independent predictor of history of systemic embolism. Age, sex, left atrial or left ventricular dimension, left ventricular ejection fraction, antiplatelet or anticoagulant therapy and the percentage of lone atrial fibrillation were not significantly different between patients with and without left atrial SEC. Among the hematologic parameters, higher hematocrit was found in patients with left atrial SEC, while white blood cell and platelet counts were comparable in both groups. Platelet aggregability with different concentrations of inducers, adenosine diphosphate and collagen, was evaluated by the turbidimetric method in 15 patients with left atrial SEC and in 42 patients without left atrial SEC who were not receiving antiplatelet or anticoagulant therapy. No significant difference was found in platelet aggregability using four inducer concentrations between two groups of patients. It is therefore concluded that SEC formation is related to the hematocrit level in patients with nonvalvular atrial fibrillation, and the results also support the hypothesis that left atrial SEC comes from erythrocyte aggregation.

Increased vagal activity promotes RAP-induced AER, which could not be totally accounted for by cholinergic effect but could be blocked by the combination of atropine and VIP antagonist. Vagally released VIP may have important role in the vagal promotion of AER.