Heart rate variability during the AVD-Glittre test in individuals with sickle cell anemia

Abstract

Introduction: Cardiovascular disease is increasingly recognized as a major contributor to premature mortality in patients with sickle cell anemia (SCA). These individuals have vaso-occlusive crises that can occasionally be associated with abnormalities in the cardiac conduction system and myocardial infarction. There is growing evidence of abnormal autonomic nervous system (ANS) function in SCA, which can lead to an increased risk of sudden death. Clinical abnormalities tend to worsen with the increase in the degree of cardiovascular autonomic dysfunction. Therefore, abnormal autonomic control of peripheral vascular resistance may predispose individuals with SCA to prolonged vasoconstriction in response to stressful stimuli and exacerbate ANS changes. In this sense, the Glittre Activities of Daily Living Test (GA-T) was developed to address the need for a broader and more representative objective assessment of functionality by involving tasks that simulate activities of daily living. Since there is growing interest in the study of heart rate variability (HRV) as a non-invasive method of assessing autonomic nervous activity in individuals with SCA, we assessed HRV during multitasking of the GA-T that encompasses both upper limb activities and lower limbs. Objective: The aim of this study was to evaluate autonomic impairment through HRV in adults with SCA during the performance of the GA-T and, secondarily, to correlate the possible abnormalities with lung capacity and respiratory and peripheral muscle function. Methods: A cross-sectional study was carried out in 16 adults with SCA aged ≥18 years and, in addition, we also evaluated 12 controls aged ≥18 years. These individuals underwent HRV analysis during the GA-T. The pulmonary function tests consisted of spirometry, measurement of the pulmonary diffusion capacity by CO (DLco) and measurement of respiratory muscle strength (RMS). Peripheral muscle function (PMF) was assessed using handgrip and quadriceps strength (QS). Results: The evaluated sample consisted of adults with SCA with a median age of 29.9 ± 8 years. In relation to controls, adults with SCA showed lower values of lung function (including RMS), handgrip and QS. In relation to the GA-T, the median time to perform tasks was 257 (198–368) seconds in adults with SCA, which was significantly longer than the time expected to complete observed in the controls. Compared to controls, adults with SCA showed lower HRV, with an emphasis on worse parasympathetic modulation by reducing the following indices: RMSSD (square root of successive differences between normal RR intervals adjacent to the square, which represents vagal modulation); pNN50 (percentage of normal RR intervals that differ more than 50 ms from its adjacent, which also represents vagal modulation); HF (high frequency of HRV, which represents parasympathetic modulation); and SD1 (standard deviation of the Poincaré graph perpendicular to the identity line, which also represents vagal activity) (P <0.001 for all). In relation to controls, adults with SCA showed greater sympathetic-vagal imbalance (increased ratio between low frequency and high frequency - LF / HF ratio) and less complexity of the ANS (decreased “approximate entropy”). The GA-T time showed significant correlations with the following parasympathetic activity indexes: RMSSD (rs = -0.650, P <0.01); pNN50 (rs = -0.932, P <0.0001), HF (rs = -0.579, P <0.01), and SD1 (rs = -0.814, P <0.0001). Additionally, we observed significant correlations between parasympathetic activity indexes and measures of DLco, handgrip and QS. Conclusion: In conclusion, adults with SCA present reduced HRV, with low parasympathetic activity, sympathetic-vagal imbalance and changes in the complexity of the ANS. Furthermore, the decrease in HRV is associated with a longer GA-T time, greater damage in pulmonary diffusion and muscle strength dysfunction.