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

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

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

Background-Normal coronary blood flow is principally determined by a backward-traveling decompression (suction) wave in diastole. Dyssynchronous chronic heart failure may attenuate suction, because regional relaxation and contraction overlap in timing. We hypothesized that biventricular pacing, by restoring left ventricular (LV) synchronization and improving LV relaxation, might increase this suction wave, improving coronary flow. Method and Results-Ten patients with chronic heart failure (9 males; age 65 +/- 12; ejection fraction 26 +/- 7%) with left bundle-branch block (LBBB; QRS duration 174 +/- 18 ms) were atriobiventricularly paced at 100 bpm. LV pressure was measured and wave intensity calculated from invasive coronary flow velocity and pressure, with native conduction (LBBB) and during biventricular pacing at atrioventricular (AV) delays of 40 ms, 120 ms, and separately preidentified hemodynamically optimal AV delay. In comparison with LBBB, biventricular pacing at separately preidentified hemodynamically optimal AV delay (BiV-Opt) enhanced coronary flow velocity time integral by 15% (7%-25%) (P = 0.007), LV dP/dt(max) by 15% (10%-21%) (P = 0.005), and (neg)dP/dt(max) by 17% (9%-22%) (P = 0.005). The cumulative intensity of the diastolic backward decompression (suction) wave increased by 26% (18%-54%) (P = 0.005). The majority of the increase in coronary flow velocity time integral occurred in diastole (69% [41%-84%]; P = 0.047). The systolic compression waves also increased: forward by 36% (6%-49%) (P = 0.022) and backward by 38% (20%-55%) (P = 0.022). Biventricular pacing at AV delays of 120 ms generated a smaller LV dP/dt(max) (by 12% [5%-23%], P = 0.013) and (neg)dP/dt(max) (by 15% [8%-40%]; P = 0.009) increase than BiV-Opt, against LBBB as reference; BiV-Opt and biventricular pacing at AV delays of 120 ms were not significantly different in coronary flow velocity time integral or waves. Biventricular pacing at AV delays of 40 ms was no different from LBBB. Conclusions-When biventricular pacing improves LV contraction and relaxation, it increases coronary blood flow velocity, predominantly by increasing the dominant diastolic backward decompression (suction) wave. (Circulation. 2012;126:1334-1344.