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Heart Rate Variability for the Early Detection of Cardiac Autonomic Dysfunction in Type 1 Diabetes

ABSTRACT: Type 1 diabetes mellitus (T1DM) has an important impact on morbidity and mortality because it may start early in life. Therefore, the early detection of cardiovascular autonomic neuropathy (DCAN) in T1DM patients is important to intervene quickly and prevent further deterioration. Traditional autonomic function tests detect abnormalities in severely symptomatic patients but they are difficult to be standardized, require the patient’s active participation and their sensitivity to the early disease is limited. In comparison, heart rate variability (HRV) is easier to be measured and standardized. Therefore, we aim to find the HRV indexes that better identify DCAN at an early stage in T1DM patients, and evaluate if HRV is a valid alternative to traditional tests. For this aim, we administered the SCOPA-AUT questionnaire on symptoms of autonomic dysfunction as well as deep breathing, Valsalva, handgrip, head-up tilt (HUT), and cold-pressor tests, to 52 T1DM patients and 27 controls. We calculated HRV indexes during supine rest (SUP) and HUT, assessing differences between groups and postures by a linear mixed-effect model for repeated measures. Receiver Operating Characteristic (ROC) analysis quantified how each HRV index and autonomic test distinguishes between patients and controls. We found that the SCOPA-AUT score was slightly but significantly (p < 0.05) greater in patients, indicating an early DCAN. T1DM patients preserved the HRV response to changing posture but in SUP they showed significantly lower standard deviation and vagal indexes of HRV than controls. The area under the ROC curve of these HRV indexes was not lower than 0.68. By contrast, traditional autonomic tests did not differ between groups. Therefore, early DCAN initially causes an impairment of the cardiac vagal control manifest in conditions of elevated vagal tone, as in SUP. Compensatory adjustments of the sympathetic control might explain the unaltered response to traditional autonomic tests. In conclusion, vagal HRV indexes in SUP help to identify early DCAN better than traditional tests, potentially allowing rapid interventions.

SUBMITTER: Castiglioni P

PROVIDER: S-EPMC9281578 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveThe aim of this study was to assess age-related changes in cardiac autonomic modulation and heart rate variability (HRV) and their association with spontaneous and pharmacologically induced vulnerability to cardiac arrhythmias, to verify the translational relevance of mouse models for further in-depth evaluation of the link between autonomic changes and increased arrhythmic risk with advancing age.MethodsHeart rate (HR) and time- and frequency-domain indexes of HRV were calculated from Electrocardiogram (ECG) recordings in two groups of conscious mice of different ages (4 and 19 months old) (i) during daily undisturbed conditions, (ii) following peripheral β-adrenergic (atenolol), muscarinic (methylscopolamine), and β-adrenergic + muscarinic blockades, and (iii) following β-adrenergic (isoprenaline) stimulation. Vulnerability to arrhythmias was evaluated during daily undisturbed conditions and following β-adrenergic stimulation.ResultsHRV analysis and HR responses to autonomic blockades revealed that 19-month-old mice had a lower vagal modulation of cardiac function compared with 4-month-old mice. This age-related autonomic effect was not reflected in changes in HR, since intrinsic HR was lower in 19-month-old compared with 4-month-old mice. Both time- and frequency-domain HRV indexes were reduced following muscarinic, but not β-adrenergic blockade in younger mice, and to a lesser extent in older mice, suggesting that HRV is largely modulated by vagal tone in mice. Finally, 19-month-old mice showed a larger vulnerability to both spontaneous and isoprenaline-induced arrhythmias.ConclusionThe present study combines HRV analysis and selective pharmacological autonomic blockades to document an age-related impairment in cardiac vagal modulation in mice which is consistent with the human condition. Given their short life span, mice could be further exploited as an aged model for studying the trajectory of vagal decline with advancing age using HRV measures, and the mechanisms underlying its association with proarrhythmic remodeling of the senescent heart.

Project description:BackgroundIron overload cardiomyopathy remains the major cause of death in patients with transfusion-dependent thalassemia. Cardiac T2* magnetic resonance imaging is costly yet effective in detecting cardiac iron accumulation in the heart. Heart rate variability (HRV) has been used to evaluate cardiac autonomic function and is depressed in cases of thalassemia. We evaluated whether HRV could be used as an indicator for early identification of cardiac iron deposition.MethodsOne hundred and one patients with transfusion-dependent thalassemia were enrolled in this study. The correlation between recorded HRV and hemoglobin, non-transferrin bound iron (NTBI), serum ferritin and cardiac T2* were evaluated.ResultsThe median age was 18 years (range 8-59 years). The patient group with a 5-year mean serum ferritin >5,000 ng/mL included significantly more homozygous β-thalassemia and splenectomized patients, had lower hemoglobin levels, and had more cardiac iron deposit than all other groups. Anemia strongly influenced all domains of HRV. After adjusting for anemia, neither serum ferritin nor NTBI impacted the HRV. However cardiac T2* was an independent predictor of HRV, even after adjusting for anemia. For receiver operative characteristic (ROC) curve analysis of cardiac T2* ≤20 ms, only mean ferritin in the last 12 months and the average of the standard deviation of all R-R intervals for all five-minute segments in the 24-hour recording were predictors for cardiac T2* ≤20 ms, with area under the ROC curve of 0.961 (p<0.0001) and 0.701 (p = 0.05), respectively.ConclusionsHemoglobin and cardiac T2* as significant predictors for HRV indicate that anemia and cardiac iron deposition result in cardiac autonomic imbalance. The mean ferritin in the last 12 months could be useful as the best indicator for further evaluation of cardiac risk. The ability of serum ferritin to predict cardiac risk is stronger than observed in other thalassemia cohorts. HRV might be a stronger predictor of cardiac iron in study populations with lower somatic iron burdens and greater prevalence of cardiac iron deposition.

Project description:Introduction: Heart Rate Variability (HRV) and Pulse Rate Variability (PRV), are non-invasive techniques for monitoring changes in the cardiac cycle. Both techniques have been used for assessing the autonomic activity. Although highly correlated in healthy subjects, differences in HRV and PRV have been observed under various physiological conditions. The reasons for their disparities in assessing the degree of autonomic activity remains unknown. Methods: To investigate the differences between HRV and PRV, a whole-body cold exposure (CE) study was conducted on 20 healthy volunteers (11 male and 9 female, 30.3 ± 10.4 years old), where PRV indices were measured from red photoplethysmography signals acquired from central (ear canal, ear lobe) and peripheral sites (finger and toe), and HRV indices from the ECG signal. PRV and HRV indices were used to assess the effects of CE upon the autonomic control in peripheral and core vasculature, and on the relationship between HRV and PRV. The hypotheses underlying the experiment were that PRV from central vasculature is less affected by CE than PRV from the peripheries, and that PRV from peripheral and central vasculature differ with HRV to a different extent, especially during CE. Results: Most of the PRV time-domain and Poincaré plot indices increased during cold exposure. Frequency-domain parameters also showed differences except for relative-power frequency-domain parameters, which remained unchanged. HRV-derived parameters showed a similar behavior but were less affected than PRV. When PRV and HRV parameters were compared, time-domain, absolute-power frequency-domain, and non-linear indices showed differences among stages from most of the locations. Bland-Altman analysis showed that the relationship between HRV and PRV was affected by CE, and that it recovered faster in the core vasculature after CE. Conclusion: PRV responds to cold exposure differently to HRV, especially in peripheral sites such as the finger and the toe, and may have different information not available in HRV due to its non-localized nature. Hence, multi-site PRV shows promise for assessing the autonomic activity on different body locations and under different circumstances, which could allow for further understanding of the localized responses of the autonomic nervous system.

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Heart Rate Variability for the Early Detection of Cardiac Autonomic Dysfunction in Type 1 Diabetes

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