Derek J. Dosdall and Raymond E. Ideker

Chapter Outline

Mechanisms of VT Onset and Maintenance

Although cases of idiopathic VF have been reported, most patients with VT and VF have a substrate that increases the probability of reentry. Two primary conditions lead to the onset of VT: ectopic foci and stable reentrant circuits. Ectopic foci due to triggered activity or abnormal automaticity may lead to VT. VT may be hemodyamically stable or unstable and often self-terminates, whereas VF is almost always fatal if not treated by administration of defibrillation shocks within minutes of VF onset. Ventricular tachyarrhythmias often progress from premature ventricular complexes (PVCs) to runs of VT, and finally to VF (Figure 48-1). Ventricular tachycardia and heart failure lead to action potential duration (APD) shortening, and rapid activation rates may lead to intracellular calcium overload. High intracellular calcium and APD shortening promote triggered activity and the initiation of VF.⁴

Focal sources that may lead to VT include triggered activity and abnormal automaticity. Focal sources may be the source of repetitive rapid ectopic firing or they may lead to disruption of the normal conduction pathways and the breakup of cohesive wave fronts and establishment of reentrant circuits (Figure 48-2, A). Delayed afterdepolarizations (DADs) cause a rise in resting potential during diastole. If the transmembrane potential rises above the activation threshold, a new action potential may be launched. DADs are traditionally linked to intracellular calcium overload and thus are exacerbated by the rapid heart rates seen in VT and VF. Early afterdepolarizations (EADs) may occur during the plateau (phase 2) or repolarization (phase 3) phase of an action potential. EADs are often associated with bradycardia or slow heart rate and have been linked to numerous ion channel disturbances including L-type calcium, rectifier potassium, and late sodium currents. The sodium/calcium exchanger current is thought to play a critical role in the development of EADs. Chua et al performed optical mapping of tachycardia-induced heart failure and demonstrated that heterogeneous up-regulation of apamin-sensitive K⁺ current increases sensitivity to intracellular calcium.⁵ This leads to heterogeneous APD shortening and possibly to late phase 3 EADs in the context of high heart rate or post-defibrillation recovery. Stretch activation may play a role in ventricular arrhythmias, particularly in the context of severe heart failure and volume overload.⁶ Abnormal automaticity consists of abnormal spontaneous firing action potentials that are not coupled to previous activations.

Stable reentrant circuits around an anatomic anchor such as a scar or a large vessel may lead to sustained VT (see Figure 48-2, A). A section of unexcitable post-infarct scar or a large vessel such as the aorta or the right ventricular (RV) outflow tract may form a pathway for a stable reentrant circuit. Even without an unexcitable core, simulations have shown that a reentrant circuit may be formed around a functional core rather than an anatomic core (see Figure 48-2, A). The center of the circuit may remain excitable but unexcited as the spiral wave circles around the core. Large reentrant circuits that encircle the entire ventricles have been shown to form as well, especially with cardiac dilatation or conduction slowing.

The reentry wavelength is the product of the conduction velocity and the distance of the path of the reentrant circuit. Ischemia, fibrosis, cellular uncoupling, and electrolyte imbalance may cause conduction slowing. Cardiac dilatation leads to greater distances for wave-front conduction. When these changes occur heterogeneously over the cardiac tissue, conduction slowing may be present to such an extent that slowed conduction in one region may lead to fractionation of a single wave front. The faster-moving portions of the wave front move around the region that has slowed conduction. If the region of slowed conduction delays the wave front for an extended time, the tissue past the area of slowed conduction may have sufficient time to become excitable. As the excitation wave front leaves the region of slowed conduction, it may travel rapidly through the normal area back around to the area of slowed conduction that activated initially. If this tissue is now excitable, the wave front may reenter into the area of slowed conduction, and the process may start again and establish a stable reentrant circuit.

Transition From VT to VF

Heterogeneous conduction leads to the breakup of continuous activation wave fronts, the development of sustained reentrant circuits, and the development of sustained VF. Critically timed focal activations may break up regular rotors and cause wave-front collisions and conduction block, leading to breakup of the regularly repeating wave fronts.

A primary mechanism for block leading to reentry is nonuniform dispersion of refractoriness. A study by Geizer et al reported that a series of premature stimuli that induced large spatial dispersion of repolarization caused VF in an in vivo dog model.⁷ This study and others have shown that block can occur even in normal, homogeneous tissue when alternans is caused in APD. Dispersion in APD leads to the development of conduction block and to fractionation of wave fronts, which, in turn, may lead to reentrant circuits and the initiation of VT and VF (Figure 48-3).

Simulations have shown that the restitution curve (the relationship between APD and the diastolic interval) is predictive of the breakdown of a rotor to multiple unstable reentrant circuits. When the slope of the restitution curve (APD/diastolic interval [DI]) is greater than 1, an unstable positive-feedback loop results in increasing oscillations in APD and DI (Figure 48-4). Once the APD and the DI become so shortened that conduction is not possible, the wave front blocks and reentry may occur. A slope of less than 1 of the restitution curve leads to a negative-feedback loop, decreasing alternans, and to convergence of cycle length and DI to an equilibrium.

VF Maintenance