Comparison of different invasive hemodynamic methods for AV delay optimization in patients with cardiac resynchronization therapy: implications for clinical trial design and clinical practice

Abstract

Background: Reproducibility and hemodynamic efficacy of optimization of AV delay (AVD) of cardiac resynchronization therapy (CRT) using invasive LV dp/dtmax are unknown.

Method and results: 25 patients underwent AV delay (AVD) optimisation twice, using continuous left ventricular (LV) dp/dtmax, systolic blood pressure (SBP) and pulse pressure (PP). We compared 4 protocols for comparing dp/dtmax between AV delays: We assessed for dp/dtmax, LVSBP and LVPP, test-retest reproducibility of the optimum. Optimization using immediate absolute dp/dtmax had poor reproducibility (SDD of replicate optima=41 ms; R(2)=0.45) as did delayed absolute (SDD 39 ms; R(2)=0.50). Multiple relative had better reproducibility: SDD 23 ms, R(2)=0.76, and (p<0.01 by F test). Compared with AAI pacing, the hemodynamic increment from CRT, with the nominal AV delay was LVSBP 2% and LVdp/dtmax 5%, while CRT with pre-determined optimal AVD gave 6% and 9% respectively.

Conclusions: Because of inevitable background fluctuations, optimization by absolute dp/dtmax has poor same-day reproducibility, unsuitable for clinical or research purposes. Reproducibility is improved by comparing to a reference AVD and making multiple consecutive measurements. More than 6 measurements would be required for even more precise optimization--and might be advisable for future study designs. With optimal AVD, instead of nominal, the hemodynamic increment of CRT is approximately doubled.

Keywords: Atrioventricular delay optimization; Biventricular pacing; Cardiac resynchronization therapy; Hemodynamic optimization; Reproducibility.

Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Figures

Fig. 1

Description of the four tested protocols for processing the dp/dtmax signal for AV delay optimization. (a) Immediate absolute LV dp/dtmax protocol: mean of a 10 second recording commenced immediately after a transition to the tested AV delay (not compared to a reference setting). (b) Delayed absolute LV dp/dtmax protocol: mean of a 10 second recording commenced after a 30 second stabilisation period following the transition to the tested AV delay. (c) Single relative LV dp/dtmax protocol: the relative change in LV dp/dtmax measured with a single transition between a reference AV delay (120 ms) and the tested AV delay. (4) Multiple relative LV dp/dtmax: the mean relative change in LV dp/dtmax calculated from a total of six transitions to and from the tested AV delay (three forward transitions to the tested AV delay and three back transitions to the reference AV delay, reversing the sign for the back transitions).

Fig. 2

Method for calculating scatter and curvature which are the biological determinants of the reproducibility of the optimum AV delay. Data from one patient is shown in order to describe how Scatter and Curvature can be calculated. Scatter is the spontaneous variability in measurements and is calculated as the standard deviation of the repeated measurements (shown in panel a). Curvature expresses how quickly the underlying measurement declines with distance away from the optimum. It is approximately parabolic and it is possible to calculate the underlying curvature by measuring the change in the acute hemodynamic parameter occurring over a known change in AV delay (panel b). The scatter:curvature ratio is calculated for each tested hemodynamic parameter in order to compare precision when used for AVD optimisation. The ratio between scatter and curvature is the biological determinant of the test–retest variability of the optimum: higher ratios indicate greater variability (panel c). SD: standard deviation.

Fig. 3

Same day reproducibility of AV delay optimization, using the four tested protocols for processing left ventricular dp/dtmax. Line of equivalence (dashed line) is displayed.

Fig. 4

Agreement with each other with regard to AV delay determined as optimal, for the 4 different protocols tested for processing LV dp/dtmax.

Fig. 5

Test–retest agreement with regard to the AV delay determined as optimal for three tested invasive hemodynamic measures. We used the multiple relative protocol to process the hemodynamic signals.

Fig. 6

Hemodynamic consequence of progressively programming the AV delay longer or shorter than optimal. In order to minimise bias we used separate measurements to identify the optimal AV delay from those used to measure the hemodynamic consequences of programming a longer or shorter AV delay.