Electrocardiographic Response of Digoxin‐Toxic Fascicular Tachycardia to Fab Fragments: Implications for Tachycardia Mechanism

Abstract

The electrocardiographic response of digoxin-induced fascicular tachycardia to Fab fragments was evaluated in two patients. In addition, we documented the response of the fascicular tachycardia to spontaneous premature ventricular depolarizations during different tachycardia rates, the response to a nonsustained episode of ventricular tachycardia, and the mode of spontaneous initiation and termination of short-lived episodes of the tachycardia during the treatment process. The following findings were noted: slowing of the tachycardia in response to Fab administration; change in the morphologic characteristics of the tachycardia from multiform to uniform; resetting of the tachycardia by spontaneous premature ventricular depolarization with the return cycle equal to the observed tachycardia cycle length; acceleration of the tachycardia in response to five beats of a faster nonsustained ventricular tachycardia; and initiation and termination of the tachycardia, both by spontaneously occurring premature ventricular depolarizations and in the absence of premature ventricular depolarizations. Both tachycardias resolved completely within 20 and 40 minutes, respectively, of Fab administration. We conclude that Fab administration can promptly resolve fascicular tachycardias precipitated by digoxin toxicity and that the observed electrocardiographic phenomena strongly suggest triggered activity as the electrophysiologic mechanism of fascicular tachycardia in man.

ECG Clues for Diagnosing Ventricular Tachycardia Mechanism

“…Delayed afterdepolarizations (DADs) occur during phase IV of the action potential, are more dependent on faster heart rates, and have been shown to be mechanistically responsible for many forms of outflow tract tachycardia and VT associated with digitalis toxicity. [7][8][9] Reentrant ventricular tachycardia requires a specific electrophysiologic substrate or milieu: (1) unidirectional conduction, (2) conduction block, either fixed or functional, and (3) a region of "slow conduction" in which the cycle length of the tachycardia is longer than the longest refractory period in the circuit. Reentrant ventricular tachycardias are often seen in structurally abnormal myocardium characterized by scarring due to ischemic or nonischemic insults.…”

“…12 We were able to evaluate the mechanism of digitalis-induced VT in 2 patients after the administration of Fab fragment. 8 Figure 5A (two leads) and B (12 leads) show surface ECG recordings from 2 patients with sustained ventricular tachycardia in the setting of digoxin toxicity. Both patients received Fab fragments to bind Digoxin under continuous ECG monitoring.…”

“…Early afterdepolarizations (EADs) occur during phase II or III of the action potential, are more manifest at slower rates, and have been shown to be mechanistically responsible for many forms of drug and electrolyte‐induced Torsades de Pointes, and some forms of polymorphic VT due to congenital long QT syndrome. Delayed afterdepolarizations (DADs) occur during phase IV of the action potential, are more dependent on faster heart rates, and have been shown to be mechanistically responsible for many forms of outflow tract tachycardia and VT associated with digitalis toxicity 7–9 …”

“…Though numerous experimental animal models support triggered activity as the mechanism of VT in digitalis toxicity, the evidence in humans has been harder to obtain 12 . We were able to evaluate the mechanism of digitalis‐induced VT in 2 patients after the administration of Fab fragment 8 Figure 5A (two leads) and B. (12 leads) show surface ECG recordings from 2 patients with sustained ventricular tachycardia in the setting of digoxin toxicity.…”

Andersen–Tawil Syndrome

“…Clinically, BVT caused by digoxin toxicity is considered an example of TA. 70 Catecholamines can cause DADs by causing intracellular Ca 2+ overload via an increase in I Ca-L and the Na + /Ca 2+ exchange current, among other mechanisms. Ischemia-induced DADs are thought to be mediated by the accumulation of lysophosphoglycerides in the ischemic tissue, 71 with subsequent elevation in Na + and Ca 2+ .…”