When is an optimization not an optimization? Evaluation of clinical implications of information content (signal-to-noise ratio) in optimization of cardiac resynchronization therapy, and how to measure and maximize it

Abstract

Impact of variability in the measured parameter is rarely considered in designing clinical protocols for optimization of atrioventricular (AV) or interventricular (VV) delay of cardiac resynchronization therapy (CRT). In this article, we approach this question quantitatively using mathematical simulation in which the true optimum is known and examine practical implications using some real measurements. We calculated the performance of any optimization process that selects the pacing setting which maximizes an underlying signal, such as flow or pressure, in the presence of overlying random variability (noise). If signal and noise are of equal size, for a 5-choice optimization (60, 100, 140, 180, 220 ms), replicate AV delay optima are rarely identical but rather scattered with a standard deviation of 45 ms. This scatter was overwhelmingly determined (ρ = −0.975, P < 0.001) by Information Content, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$ {\frac{\text{Signal}}{{{\text{Signal}} + {\text{Noise}}}}} $$\end{document}, an expression of signal-to-noise ratio. Averaging multiple replicates improves information content. In real clinical data, at resting, heart rate information content is often only 0.2–0.3; elevated pacing rates can raise information content above 0.5. Low information content (e.g. <0.5) causes gross overestimation of optimization-induced increment in VTI, high false-positive appearance of change in optimum between visits and very wide confidence intervals of individual patient optimum. AV and VV optimization by selecting the setting showing maximum cardiac function can only be accurate if information content is high. Simple steps to reduce noise such as averaging multiple replicates, or to increase signal such as increasing heart rate, can improve information content, and therefore viability, of any optimization process.

Rate-adaptive AV delay and exercise performance following cardiac resynchronization therapy

“…Mokrani et al demonstrated a difference in the optimal AV delay at rest and on exercise depending on whether LVOT VTI or maximum LVFT was employed. (10) Using the iterative method, the exact mechanism that the operator is attempting to manipulate, (timing of ventricular filling) is viewed directly, rather than employing a surrogate outcome measure such as LVOT VTI, which is subject to significant variation due to small changes in the angle between the incident ultrasound beam and the outflow tract with respiration, an effect particularly exaggerated during exercise (23,24). As the maximum improvement in cardiac output with AV delay optimization is in the region of 15-20% (1), any technique with a reported reproducibility of 4-10% during optimal resting conditions should be interpreted with caution during exercise, and may underlie the reported mixed results using these methods (5,6,10).…”

Improvement in Coronary Blood Flow Velocity With Acute Biventricular Pacing Is Predominantly Due to an Increase in a Diastolic Backward-Travelling Decompression (Suction) Wave

“…This permits the relative systolic blood pressure difference between the tested AV delay and reference AV to be determined to high precision. 23,28 The AV delays tested for each patient ranged from 40, 80, 160, 200, 240 ms, and so forth, until intrinsic AV conduction was reached with evidence of LBBB. Parabolic curve fitting was used to improve the precision of determination of the optimum.…”

Vectorcardiography as a Tool for Easy Optimization of Cardiac Resynchronization Therapy in Canine Left Bundle Branch Block Hearts

“…Disadvantages of these procedures are that they are time consuming, complicated, expensive, and may even be inaccurate. 1 In a previous study we have shown that optimal LV systolic function can be predicted using mechanical interventricular dyssynchrony (MIVD). 2 In that study, performed in canine LBBB hearts as well as in CRT patients, a MIVD value halfway between its minimal (LV pacing with short AV delay) and maximal value (during LBBB or RV pacing) coincided with optimal systolic function.…”