Key result
Phase-dependent time normalization using isophase lines predicted pressure curves with higher accuracy than isochrones (RMSE 3.8 vs 14.0 mmHg, P<0.001).
Phase-dependent time normalization reduces cardiac load dependency of timing and increases accuracy in estimating time-varying elastance in a preclinical model.
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May refine elastance estimation in animal models; leaves open human validation of isophase normalization.
The time-varying elastance concept provides a comprehensive description of the intrinsic mechanical properties of the left ventricle that are assumed to be load independent. Based on pressure-volume measurements obtained with combined pressure conductance catheterization in six open-chest anesthetized sheep, we show that the time to reach end systole (defined as maximal elastance) is progressively prolonged for increasing ventricle pressures, which challenges the original (load-independent) time-varying elastance concept. Therefore, we developed a method that takes into account load dependency by normalization of time course of the four cardiac phases (isovolumic contraction, ejection, isovolumic relaxation, filling) individually. With this normalization, isophase lines are obtained that connect points in pressure-volume loops of different beats at the same relative time in each of the four cardiac phases, instead of isochrones that share points at the same time in a cardiac cycle. The results demonstrate that pressure curves can be predicted with higher accuracy, if elastance curves are estimated using isophase lines instead of using isochrones [root-mean-square error (RMSE): 3.8 +/- 1.0 vs. 14.0 +/- 7.4 mmHg (P < 0.001), and variance accounted for (VAF): 94.8 +/- 1.3 vs. 78.6 +/- 14.8% (P < 0.001)]. Similar results were found when the intercept volume was assumed to be time varying [RMSE: 1.7 +/- 0.3 vs. 13.4 +/- 7.4 mmHg (P < 0.001), and VAF: 97.4 +/- 0.5 vs. 81.8 +/- 15.5% (P < 0.001)]. In conclusion, phase-dependent time normalization reduces cardiac load dependency of timing and increases accuracy in estimating time-varying elastance.
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Kind et al. (2008) studied this question. Phase-dependent time normalization (isophase lines) vs. Isochrones was evaluated on Root-mean-square error (RMSE) of predicted pressure curves (p=< 0.001). Phase-dependent time normalization using isophase lines predicted pressure curves with higher accuracy than isochrones (RMSE 3.8 vs 14.0 mmHg, P<0.001).
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