Impact of local ablation on interconnected channels within ventricular scar: mechanistic implications for substrate modification.

BACKGROUND: The extent to which channels within scar are interconnected is not known. The objective of the study was to evaluate the impact of local ablation of late potentials (LPs) on adjacent and remote areas of slow conduction with simultaneous multipolar mapping. METHODS AND RESULTS: Analysis was performed on consecutive patients referred for ablation of scar-mediated ventricular tachycardia with double ventricular access. Ablation was performed targeting the earliest of LPs visualized on the multipolar catheter, and the impact on later LPs was recorded. In 21 patients, a multipolar catheter placed within scar visualized spatially distinct LPs. Among 39 radiofrequency applications, ablation at earlier LPs had an effect on neighboring and remote LPs in 31 (80%), with delay in 8 (21%), partial elimination in 9 (23%), and complete elimination in 14 (36%). The mean distance where an ablation impact was detected was 17.6±14.7 mm (range, 2-50 mm). Among all patients, 9.7±7.8 radiofrequency applications were delivered to homogenize the targeted scar region with a mean number of 23±12 LPs targeted. CONCLUSIONS: Ablation can eliminate neighboring and remote areas of slow conduction, suggesting that channels within scar are frequently interconnected. This is the first mechanistic demonstration to show that ablation can modify electrical activity in regions of scar outside of the known radius of an radiofrequency lesion. The targeting of relatively earlier LPs can expedite scar homogenization without the need for extensive ablation of all LPs.

A novel SCN5A mutation V1340I in Brugada syndrome augmenting arrhythmias during febrile illness.

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 pathophysiological 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 hNa(v)1.5 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 degrees C and 40 degrees C. RESULTS: At 22 degrees 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 degrees C, 37 degrees C and 40 degrees C. The voltage dependency of steady-state activation was leftward shifted both in WT-delQ and V1340I-delQ at 40 degrees C. In addition, the V1340I-delQ accelerated the recovery time course from fast inactivation compared to the WT-delQ at 40 degrees 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.

Ambulatory monitoring of congestive heart failure by multiple bioelectric impedance vectors.

OBJECTIVES: This study was designed to investigate the properties of multiple bioelectric impedance signals recorded during congestive heart failure (CHF) by utilizing various electrode configurations of an implanted cardiac resynchronization therapy system. BACKGROUND: The monitoring of CHF has relied mainly on right-side heart sensors. METHODS: Fifteen normal dogs underwent implantation of cardiac resynchronization therapy systems using standard leads. An additional left atrial (LA) pressure lead sensor was implanted in 5 dogs. Continuous rapid right ventricular (RV) pacing was applied over several weeks. Left ventricular (LV) catheterization and echocardiography were performed biweekly. Six steady-state impedance signals, utilizing intrathoracic and intracardiac vectors, were measured through ring (r), coil (c), and device Can electrodes. RESULTS: Congestive heart failure developed in all animals after 2 to 4 weeks of pacing. Impedance diminished gradually during CHF induction, but at varying rates for different vectors. Impedance during CHF decreased significantly in all measured vectors: LV(r)-Can, -17%; LV(r)-RV(r), -15%; LV(r)-RA(r), -11%; RV(r)-Can, -12%; RV(c)-Can, -7%; and RA(r)-Can, -5%. The LV(r)-Can vector reflected both the fastest and largest change in impedance in comparison with vectors employing only right-side heart electrodes, and was highly reflective of changes in LV end-diastolic volume and LA pressure. CONCLUSIONS: Impedance, acquired by different lead electrodes, has variable responses to CHF. Impedance vectors employing an LV lead are highly responsive to physiologic changes during CHF. Measuring multiple impedance signals could be useful for optimizing ambulatory monitoring in heart failure patients.

Left ventricular twist mechanics in a canine model of reversible congestive heart failure: a pilot study.

BACKGROUND: Left ventricular (LV) twist dynamics play an important role in LV systolic and diastolic function. The aim of this preliminary study was to investigate LV twist dynamics in a canine model of reversible congestive heart failure (CHF). METHODS: Pacing systems were implanted in adult dogs, and continuous chronic right ventricular pacing (230-250 beats/min) was applied until CHF induction. Pacing was then stopped to allow the heart to recover. Echocardiography and LV catheterization were performed at baseline, during CHF while pacing was temporarily switched off, and during recovery. LV twist was computed as the difference between apical and basal rotation measured using 2-dimensional speckle tracking. Torsion was further calculated as LV twist divided by the LV long axis. The untwisting rate was computed as the peak diastolic time derivative of twist. RESULTS: In 6 dogs that completed the study, we found that CHF developed after 2 to 4 weeks of pacing, with LV end-diastolic volume, end-systolic volume, end-diastolic pressure, and the time constant of relaxation during isovolumic relaxation period (tau) all increasing significantly compared with baseline and recovering to normal levels 2 to 4 weeks after pacing was stopped. LV twist, torsion, and untwisting rate decreased significantly with CHF compared with baseline and improved during recovery from CHF. CONCLUSION: LV twist dynamics reflect pacing-induced CHF and its reversal as assessed by echocardiographic speckle tracking.