Epicardial Activation of Left Ventricular Wall Prolongs QT Interval and Transmural Dispersion of Repolarization

Abstract

Background-Epicardial pacing of the left ventricle (LV) has been shown to prolong the QT interval and predispose to the development of torsade de pointes arrhythmias. The present study examines the cellular basis for QT prolongation and arrhythmogenesis after reversal of the direction of activation of the LV wall. Methods and Results-A transmural ECG and transmembrane action potentials were simultaneously recorded from epicardial, M, and endocardial cells of arterially perfused canine LV wedge preparations. QT interval increased from 297.6Ϯ3.9 to 314.0Ϯ5.7 ms (nϭ12; PϽ0.001) and transmural dispersion of repolarization (TDR) increased from 35.5Ϯ5.2 to 70.3Ϯ6.2 ms (nϭ12; PϽ0.001) as pacing was shifted from endocardium to epicardium. Conduction time between M and epicardial cells increased from 12.1Ϯ1.2 to 24.2Ϯ1.5 ms (nϭ12; PϽ0.001).Amplification of TDR was further accentuated in the presence of rapidly activating delayed rectifier potassium current blockers (E-4031 and cisapride), increasing from 50.5Ϯ7.6 to 86.1Ϯ6.2 ms (nϭ8; PϽ0.01). Torsade de pointes arrhythmias could be induced during epicardial, but not endocardial, pacing of LV in the presence of rapidly activating delayed rectifier potassium current blockade. Key Words: electrocardiography Ⅲ torsade de pointes Ⅲ heart failure Ⅲ pacemakers Ⅲ electrophysiology R ecent studies have highlighted the benefits of resynchronization therapy involving biventricular pacing for patients with congestive heart failure, demonstrating enhanced cardiac output and New York Heart Association class improvement. [1][2][3][4] Despite improvements in hemodynamics and patient quality of life, the incidence of sudden death in patients treated with biventricular pacing remains high. 5,6 Recent reports document the development of R-on-T ventricular extrasystoles and ventricular tachyarrhythmias after the initiation of biventricular pacing. 7,8 Resynchronization therapy most commonly involves the placement of one stimulating catheter in the right ventricular (RV) apex and another in contact with the left ventricular (LV) epicardium via the coronary sinus. Although the mechanical benefits of resynchronization therapy have been studied extensively, little attention has been directed toward the consequences of reversing the electric activation of the LV free wall. Using a rabbit wedge preparation, Medina-Ravell et al 8 demonstrated the development of early afterdepolarizations and increased dispersion of epicardial and endocardial repolarization after reversal of the transmural sequence of activation, suggesting that these mechanisms may underlie the development of torsade de pointes in patients undergoing resynchronization therapy. Conclusions-ReversalOur laboratory first described the contribution of M cells to transmural dispersion of repolarization (TDR) in 1991 9 -11 and in more recent years has shown these cells to be the chief culprits in the development of torsade de pointes under a wide variety of conditions. 12 The present study tests the hypothesis that delayed activation and...

Cardiac Resynchronization Therapy and its Potential Proarrhythmic Effect

“…25 Similar results were reported by Medina-Ravell et al along with an increased number of R-on-T extrasystoles and episodes of torsade de pointes (TdP) with epicardial pacing. 9 The proarrhythmic potential of epicardial pacing is most likely determined by the characteristics of the altered activation sequence and the condition of the underlying substrate.…”

“…More compelling data is presented in smaller studies that elucidate the electrophysiologic impact of epicardial pacing and the potentially proarrhythmic effects of cardiac resynchronization therapy. 9,10,25 …”

“…This reversal has been shown to create heterogeneous conduction patterns and increase transmural dispersion of repolarization (TDR) in experimental models. 9,25 Such nonuniformity is an established and important determinant of reentrant arrhythmias.…”

Transseptal Leftventricular Endocardial Pacing is an Alternative Technique in Cardiac Resynchronization Therapy. One Year Experience in a High Volume Center

“…In our small study population no phrenic nerve stimulation occurred at high energy stimulation and optimal implantation and follow-up electrical parameters were observed ( Table 2). Experimental and clinical observations also indicated that LV endocardial stimulation enables a more physiological electrical activation of the left ventricle, with a transmural activation spreading from the endocardium to the epicardium [19,20]. Better hemodynamic results with higher aortic and mitral time velocity integral, improvement of LV fractional shortening and less ventricular dyssynchrony were reported with endocardial than with epicardial LV stimulation [21,22].…”

The proarrhythmic effect of cardiac resynchronization therapy: An issue that should be borne in mind

“…24 Experimental studies have shown that epicardial-endocardial conduction time is significantly longer than endocardial-epicardial conduction time, due to a zone of myocardial wall between the deep subendocardium and mid-myocardial layers. 25,26 The resulting increased dispersion of repolarization prolongs QT The proarrhythmic effect of cardiac resynchronization therapy: An issue that should be borne in mind 309.e5…”