LQT1 Genotype in Tachypaced Cardiomyopathy Causes Discordance of Baseline and VF Refractoriness

Abstract

Reduction of the slow outward rectifier (Iks) and calcium disregulation accompany tachypacing induced cardiomyopathy (TICM). While TICM Iks downregulation prolongs APD, its effect on refractoriness during VF is less clear. We used a transgenic rabbit model of Long QT 1 (LQT1) to investigate the effect of loss of Iks on VF refractoriness in TICM.Five LQT1 and littermate control rabbits underwent rapid RV pacing followed by in vivo electrophysiological studies and VF inductions. Dual voltage-calcium epicardial optical mapping was performed on whole hearts at baseline and in VF.In vivo, a strong correlation for ventricular effective refractoriness and VF interval was seen in LMC-TICM, but not in LQT1-TICM (r = 0.83 vs r = 0.36; p<0.05). Optical mapping demonstrated APD prolongation in LQT1-TICM compared to LMC-TICM (224±18ms vs. 191±15ms), but surprisingly higher VF frequencies in LQT1-TICM (15.7±0.8 vs 12.6±0.7Hz; p<0.05). In spatial VF frequency maps, LMC-TICM showed a negative VF frequency-APD map correlation (−0.43±0.24), while LQT1-TICM demonstrated a paradoxical positive correlation (0.22±0.14; p<0.05). Calcium-voltage discordance was increased in LQT1-TICM compared to controls (see fig).LQT1-TICM leads to dissociation between baseline and VF refractoriness demonstrating high frequency VF associated with calcium-voltage discordance.View Large Image | View Hi-Res Image | Download PowerPoint Slide