Critical Volume of Human Myocardium Necessary to Maintain Ventricular Fibrillation – Kedar Aras

Abnormal QT intervals, long QT or short QT, have been epidemiologically linked with sudden cardiac death due to ventricular fibrillation (VF). Consequently, Food and Drug Administration (FDA) recommends testing all pharmacological agents for “QT toxicity” as a risk factor for cardiac toxicity. Such tests assess QT/QTc interval, which represents ventricular depolarization and repolarization. However, the current QT toxicity analysis does not account for the well-known anisotropy in cardiac tissue conductivity. Mines demonstrated in 1913 that cardiac wavelength λ determines inducibility of reentrant arrhythmia, where both repolarization time or action potential duration (APD) and conduction velocity (CV) determine λ=APDxCV. We aimed to determine the role of anisotropic wavelength λ in inducibility of VF in explanted human left ventricular (LV) preparations. We tested the hypothesis that 3D cardiac wavelength, which takes into account anisotropic cardiac tissue conductivity can accurately predict VF sustainability.

Abnormal QT intervals, long QT or short QT, have been epidemiologically linked with sudden cardiac death due to ventricular fibrillation (VF). Consequently, Food and Drug Administration (FDA) recommends testing all pharmacological agents for “QT toxicity” as a risk factor for cardiac toxicity. Such tests assess QT/QTc interval, which represents ventricular depolarization and repolarization. However, the current QT toxicity analysis does not account for the well-known anisotropy in cardiac tissue conductivity. Mines demonstrated in 1913 that cardiac wavelength λ determines inducibility of reentrant arrhythmia, where both repolarization time or action potential duration (APD) and conduction velocity (CV) determine λ=APDxCV. We aimed to determine the role of anisotropic wavelength λ in inducibility of VF in explanted human left ventricular (LV) preparations. We tested the hypothesis that 3D cardiac wavelength, which takes into account anisotropic cardiac tissue conductivity can accurately predict VF sustainability.

At baseline, at pacing rate of 240 BPM, the wavelengths were: λL=9.6±0.6 cm, lTV=4.2±0.3 cm, and lTM=5.8±0.2 cm, respectively (n=7), and thus Vl=246.4±42.1 cm3. Administration of pinacidil at escalating concentrations progressively decreased Vl, and VF became sustained, when VT/Vl was above safety factor k=4.4±0.6 (n=9) during rapid pacing. Treatment with glybenclamide decreased VT/Vl below k at any pacing rate and prevented VF sustainability. Sustained VF was only sustained in ventricular volume exceeding critical wavelength volume VlLTVTM.