Repolarization Changes Underlying Long-Term Cardiac Memory Due to Right Ventricular Pacing

Abstract

Background Cardiac memory refers to the observation that altered cardiac electrical activation results in repolarization changes that persist after the restoration of a normal activation pattern. Animal studies, however, have yielded disparate conclusions both regarding the spatial pattern of repolarization changes in cardiac memory and the underlying mechanisms. This study was undertaken to produce three dimensional images of the repolarization changes underlying long-term cardiac memory in humans. Methods and Results Nine adult subjects with structurally normal hearts and dual-chamber pacemakers were enrolled in the study. Non-invasive electrocardiographic imaging (ECGI) was used before and after one month of ventricular pacing to reconstruct epicardial activation and repolarization patterns. Eight subjects exhibited cardiac memory in response to ventricular pacing. In all subjects, ventricular pacing resulted in a prolongation of the activation recovery interval (a surrogate for action potential duration) in the region close to the site of pacemaker-induced activation from 228.4±7.6 ms during sinus rhythm to 328.3±6.2 ms during cardiac memory. As a consequence, increases are observed in both apical-basal and right-left ventricular gradients of repolarization resulting in a significant increase in the dispersion of repolarization. Conclusions These results demonstrate that electrical remodeling in response to ventricular pacing in human subjects results in action potential prolongation near the site of abnormal activation and a marked dispersion of repolarization. This dispersion of repolarization is potentially arrhythmogenic and, intriguingly, was less evident during continuous RV pacing, suggesting the novel possibility that continuous RV pacing at least partially suppresses pacemaker-induced cardiac memory.

Cardiac Memory

“…16,19 Later, it was discovered that not only the transmural repolarization gradient in CM is site-specific, 20 but also other gradients exist including apical-basal and right-to-left ventricle. 21,22 There is a general agreement across the studies that CM is associated with prolongation of repolarization in the early activated areas. However, repolarization changes at the late activated sites were variable ranging from shortening, 23 minimal, or no change 20,22 to significant APD prolongation.…”

“…21,22 There is a general agreement across the studies that CM is associated with prolongation of repolarization in the early activated areas. However, repolarization changes at the late activated sites were variable ranging from shortening, 23 minimal, or no change 20,22 to significant APD prolongation. 24,25 Discrepancy in these findings is a subject of an ongoing debate and is likely related to the differences in experimental models, pacing site, species, and methods of measurement.…”

Long QT Syndrome Complicating Atrioventricular Block

“…12 (2) In patients implanted with dual chamber pacemakers because of sinus node dysfunction, reprogramming the devices to atrial pacing only, after weeks of continuous atrioventricular pacing, leads to marked QT prolongation, 21 and electrocardiographic imaging 22 confirms that (like in the animal model) cardiac memory in humans is associated with increased dispersion of repolarization across the ventricles. In all these studies, the impact of cardiac memory on QT prolongation was modest and would not be expected to be arrhythmogenic.…”

Electrical remodeling reflected by QRS and T vector changes following cardiac resynchronization therapy is related to survival in heart failure patients with left bundle branch block

“…Of note, in normal hearts undergoing abnormal activation such as RV apex pacing, intermittent LBBB or preexcitation the presence of cardiac memory has traditionally been associated with proarrhythmia and worse prognosis [14]. Marrus et al showed that in patients displaying cardiac memory, cessation of ventricular pacing results in the prolongation of the action potential (APD) of the myocytes closest to the site of pacing [6]. This increases dispersion of repolarization which in turn is known to promote arrhythmia [15].…”

“…Cardiac memory is defined as temporarily persisting changes of the T-wave axis when normal cardiac excitation is restored after a period of abnormal cardiac activation [2]. This phenomenon has been described following right ventricular pacing, cardiac resynchronization therapy, intermittent left bundle branch block, ventricular and supraventricular tachycardia or pre-excitation [3][4][5][6]. Electrical remodeling is the name for a range of ECG changes that accompany ventricular remodeling but do not fit within the strict definition of cardiac memory, such as changes in QRS complex duration or QRS vector angles.…”