Correlation between Fractal Behavior of HRV and Neurohormonal and Functional Indexes in Chronic Heart Failure

Abstract

Higher neurohormonal activation levels are known markers of severity and adverse prognosis in heart failure (HF) patients. Classical linear indexes of heart rate variability (HRV) have been shown to be associated with neurohormonal activation. Whether and to what extent non-linear properties of HRV, as expressed by the fractal dimension (FD) index, also reflect neurohormonal activation is not known. Aim of the study was to assess the association between FD, plasma norepinephrine (NPE) levels and functional parameters as compared to classical linear indexes of HRV in HF patients. Ninety-nine stable mild-to-moderate HF patients in sinus rhythm (age: 51±8 years, New York Heart Association class II-III, left ventricular ejection fraction [EF] 24±6%, maximal oxygen consumption [VO2max] during exercise tests 14±4 mL kg-1 min-1) were studied. Each patient underwent to a 24-hour Holter recording and to NPE assay within one week plasma, besides standard clinical and laboratory examinations. The standard deviation between normal to normal beats (SDNN) and the power in the low frequency band (LFP, 0.04-0.15 Hz) were computed on consecutive 5-min RR sequences. The FD was estimated by the Higuchi method. The association between HRV and neurohormonal and functional indexes was assessed by Spearman correlation coefficient. NPE, LFP, SDNN and FD were respectively (mean ± SD): 363±210 pg/l, 162±171 ms2, 36±15 ms and 1.6±0.1. Both SDNN and LFP showed a moderate but significant negative correlation with NPE levels (r=-0.37 and -0.44 respectively, p<0.0001 for both); FD exhibited a weaker association (r=0.29, p<0.005). Linear indexes were significantly associated with VO2max (r=0.31 and 0.36 respectively, p<0.001), while FD showed a negative correlation of similar magnitude (r=-0.34, p<0.001). Similar relationships were found with EF (r=0.34, 0.35 and -0.42 for SDNN, LFP and FD, respectively, p<0.001 for all). These findings suggest that although the association of linear and fractal dimension HRV indexes with functional parameters is similar, the former, particularly the power in the low frequency band, appears to reflect more closely the level of adrenergic activation of HF patients.