Evaluating multisite pacing strategies in cardiac resynchronization therapy in the preclinical setting

Abstract

BACKGROUND Multisite pacing strategies that improve response to cardiac resynchronization therapy (CRT) have been proposed. Current available options are pacing 2 electrodes in a multipolar lead in a single vein (multipoint pacing [MPP]) and pacing using 2 leads in separate veins (multizone pacing [MZP]).OBJECTIVE The purpose of this study was to compare in a systematic manner the acute hemodynamic response (AHR) and electrophysiological effects of MPP and MZP and compare them with conventional biventricular pacing (BiVP).METHODS Hemodynamic and electrophysiological effects were evaluated in a porcine model of acute left bundle branch block (LBBB) (n 5 8). AHR was assessed as LVdP/dtmax. Activation times were measured using .100 electrodes around the epicardium, measuring total activation time (TAT) and left ventricular activation time (LVAT).RESULTS Compared to LBBB, BiVP, MZP, and MPP reduced TAT by 26% 6 10%, 32% 6 13%, and 32% 6 14%, respectively (P 5 NS between modes) and LVAT by 4% 6 5%, 11% 6 5%, and 12% 6 5%, respectively (P ,.05 BiVP vs MPP and MZP). On average, BiVP increased LVdP/dtmax by 8% 6 4%, and optimal BiVP increased LVdP/dtmax by 13% 6 4%. The additional improvement in LVdP/ dtmax by MZP and MPP was significant only when its increase during BiVP and decrease in TAT were poor (lower 25% of all sites in 1 subject). The increase in LVdP/dtmax was larger when large interelectrode distances (.5 cm vs ,2.2 cm) were used.CONCLUSION In this animal model of acute LBBB, MPP and MZP create similar degrees of electrical resynchronization and hemodynamic effect, which are larger if interelectrode distance is large. MPP and MZP increase the benefit of CRT only if the left ventricular lead used for BiVP provides poor response.

Determinants of LV dP/dtmaxand QRS duration with different fusion strategies in cardiac resynchronisation therapy

“… 20 Our study MPP provided shorter QRSd than pacing from single electrodes, suggesting that shortening of QRSd in our study also reflects the shortening of the left ventricular activation time. 10 If shortening of QRSd were to be the sole target for a response; however, our data suggest that this will come at the cost of not optimising LV dP/dt max and vice versa. Concurrently, QRSd may not shorten to the most considerable extent with CRT when pacing LV from sites that reflect the maximal mechanical response.…”

“… 8 The fact that LV dP/dt max does not necessarily reflect better resynchronisation may also explain why MPP that increase LV dP/dt max and shorten QRSd acutely failed to show a clinical benefit compared with conventional BIVP in the MOre REsponse to Cardiac Resynchronization Therapy with Multi-Point Pacing (MORE-CRT) study. 10 11 19 The predictive value of an increase in LV dP/dt max from baseline for determining the response to CRT is weak. It seems that fusion and LV pre-excitation, inevitably linked to CRT, contribute independently to a rise in LV dP/dt max and a change in QRSd.…”

“…Multisite pacing with a larger electrode separation could have provided an even more apparent LV pre-excitation effect. 10 Placement of the RV and LV electrodes in close proximity could have affected the degree of fusion and pre-excitation resulting from LV activation. Of the patients in this study, 16% were classified as not having true LBBB, and fusion with intrinsic conduction in such patients may be different from fusion with LBBB.…”

“…1 2 CRT causes improved electrical synchrony (shortened QRS duration (QRSd)) and mechanical function (higher left ventricular (LV) dP/dt max ) once inserted. 3 4 Research groups have therefore used LV dP/dt max and QRSd to guide different approaches to improve CRT, [4][5][6][7][8][9][10] including fusion of intrinsic conduction with paced wavefronts and LV pre-excitation. 7 9 11-14 The objective of this study was to analyse how fusion determines LV dP/dt max and QRSd to understand better how these measurements reflect resynchronisation and should be interpreted if they were to be used for acute haemodynamic…”

To the Editor — Multisite pacing strategies: Solutions looking for a problem?

“…Multipole (pacing from multiple electrodes on the same lead) and multipoint (pacing from 2 electrodes on different leads) studies, where initiating activation from multiple locations in the left ventricle (LV), is proposed to achieve a more synchronous activation and improve CRT response. Consistent with this synchronous activation hypothesis, the recent study by Heckman et al 1 finds that pacing from widely separated electrodes was beneficial and that no change in total activation time with multipole/multipoint pacing caused no improvement in acute hemodynamic response. However, while changes in LV activation times were reported in the abstract, their relationship with the acute hemodynamic response was not explored.…”