Short- and Long-Range Correlations in Beat Rate Variability of Human Pluripotent-Stem-Cell-Derived Cardiomyocytes

Abstract

A healthy heart exhibits fractal, i.e., long-range correlated fluctuations in heart rate variability (HRV). It is recently shown that fractal dynamics is also an intrinsic feature of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). In this study, we investigate short-and long-range correlations in beat rate variability (BRV) of hiPSC-CMs, obtained from a healthy subject and symptomatic and asymptomatic long QT syndrome patients. It is shown that it is important to distinguish correlation properties in short and long time scales, as the scaling exponents are significantly different and also behave differently in the acute exposure to pharmacological compounds that modulate β1-adrenoreceptors and cardiac ion channel generating delayed, outwardly rectifying K + current (I Ks ). While long-range scaling is sensitive to the drug exposure, short-range scaling is barely affected.

Intrinsic Complexity of RR and QT Intervals at the Cellular Level

“…The result indicates that the intrinsic complexity of the hiPSC-CMs can be altered by a diseased state of hiPSC-CMs. It is also in line with our previous study [16], which showed that symptomatic LQT1-CMs exhibit reduced short-term scaling exponents, while healthy and asymptomatic LQT1-CMs have scaling exponents close to 1/f noise throughout the scale.…”