Abstract—The Detrended Fluctuation Analysis (DFA) is a popular method for quantifying the self-similarity of the heart rate that may reveal complexity aspects in cardiovascular regulation. However, the self-similarity coefficients provided by DFA may be affected by an overestimation error associated with the shortest scales. Recently, the DFA has been extended to calculate the multifractal-multiscale self-similarity and some evidence suggests that overestimation errors may affect different multifractal orders. If this is the case, the error might alter substantially the multifractal-multiscale representation of the cardiovascular self-similarity. The aim of this work is 1) to describe how this error depends on the multifractal orders and scales and 2) to propose a way to mitigate this error applicable to real cardiovascular series. Clinical Relevance— The proposed correction method may extend the multifractal analysis at the shortest scales, thus allowing to better assess complexity alterations in the cardiac autonomic regulation and to increase the clinical value of DFA. I. INTRODUCTION The interest in the fractal analysis of the heart rate has been progressively growing aimed at describing the complex cardiovascular regulation, its adaptations to external stimuli and behavioral conditions, and its interactions with the autonomic control and the respiratory system. In this context, the Detrended Fluctuation Analysis (DFA) is a powerful tool for quantifying the fractal structure of cardiovascular series [1] based on the estimation of a coefficient, α, related to the Hurst's exponent. The DFA calculates the 2 nd order moment of the fluctuations of the integrated series after polynomial detrending on consecutive blocks of n beats, F(n). For fractal series, α is estimated as the slope of log F(n) vs. log n [2]. Since the heart rate shows a multiscale behavior, it has been proposed to estimate α as a function of n, α(n), by calculating "local" slopes around n [3], [4]. However, the DFA may overestimate the local slopes at the shorter scales, likely because of the overfitting of the detrending polynomial (the overestimation increases with the polynomial order) [5]. A proposed correction method assumes the same α at all the scales [5] and thus cannot be applied on real cardiovascular series because of their multiscale nature. Alternatively, it was suggested to use high-order polynomials at the larger scales, where the overfitting is negligible, and the 1 st order polynomial, which causes the lowest overfitting, at the shortest scales [6]. However, also the 1 st order detrending P. Castiglioni is with IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy (email: pcastiglioni@dongnocchi.it ). G. Parati and A. Faini are with Istituto Auxologico Italiano, IRCCS, Dept. of Cardiovascular, Neural and Metabolic Sciences Milan, Italy (email: a.faini@auxologico.it). polynomial may cause overestimations that limit the shortest analyzable n. Recently, the multiscale DFA was modified to evaluate the multifractality [7] calculating the q th moment order of the residual variances, F q (n), and the multifractal multiscale self- similarity coefficients, α(q,n), as the local slopes of log F q (n) vs. log n. It is possible that the estimation bias affecting the monofractal α also influences α(q,n) at q2, but whether the error depends on both q and n and if it alters the quantification of multifractality has never been described systematically. Therefore, this work aims to describe the estimation bias in the multifractal multiscale DFA and to propose a method applicable to real cardiovascular series for mitigating this error. II. DFA ESTIMATION BIAS A. The Multifractal Multiscale DFA The DFA evaluates the multifractality of a time series S i of N samples (i=1,...,N), with mean μ and standard deviation σ, by calculating the summation y i =∑ σ  (1), by splitting the y i series into M blocks of n samples, and by evaluating the variability function F q (n)  =     ! " ≠ 0  = % & ’ ()* +  ,-& ! " = 0 (2) with σ 2 n (k) the variance of the residuals of y i in each block k after polynomial detrending [8]. In our work, n increased linearly on a log scale from 6 up to N/4 samples. Moreover, we considered integer q between -5 and +5; maximally overlapped blocks, which means that M=N-n+1; and linear detrending. The local slopes α(q,n) were calculated as the derivative of log F q (n) vs. log n [6]. The cumulative functions of the α(q,n) squared increments were calculated separately for positive q α /0 1  = ∑ 23",  − 3" − 1, 7 8  (3) and negative q α /0  = ∑ 23",  − 3" − 1, 7 9 81 (4). The α /0 1 ) and α /0  functions represent scale-by-scale measures of the degree of multifractality [9] . Multifractal and Multiscale Detrended Fluctuation Analysis of Cardiovascular Signals: how the Estimation Bias Affects Short- Term Coefficients and a Way to mitigate this Error Paolo Castiglioni, Gianfranco Parati, and Andrea Faini 2021 43rd Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC) Oct 31 - Nov 4, 2021. Virtual Conference 978-1-7281-1178-0/21/$31.00 ©2021 IEEE 257