Short-term deceleration capacity of heart rate: a sensitive marker of cardiac autonomic dysfunction in idiopathic Parkinson's disease.

PURPOSE: Cardiac autonomic dysfunction in idiopathic Parkinson's disease (PD) manifests as reduced heart rate variability (HRV). In the present study, we explored the deceleration capacity of heart rate (DC) in patients with idiopathic PD, an advanced HRV marker that has proven clinical utility. METHODS: Standard and advanced HRV measures derived from 7-min electrocardiograms in 20 idiopathic PD patients and 27 healthy controls were analyzed. HRV measures were compared using regression analysis, controlling for age, sex, and mean heart rate. RESULTS: Significantly reduced HRV was found only in the subcohort of PD patients older than 60 years. Low- frequency power and global HRV measures were lower in patients than in controls, but standard beat-to-beat HRV markers (i.e., rMSSD and high-frequency power) were not significantly different between groups. DC was significantly reduced in the subcohort of PD patients older than 60 years compared to controls. CONCLUSIONS: Deceleration-related oscillations of HRV were significantly reduced in the older PD patients compared to healthy controls, suggesting that short-term DC may be a sensitive marker of cardiac autonomic dysfunction in PD. DC may be complementary to traditional markers of short-term HRV for the evaluation of autonomic modulation in PD. Further study to examine the association between DC and cardiac adverse events in PD is needed to clarify the clinical relevance of DC in this population.

Increased markers of cardiac vagal activity in leucine-rich repeat kinase 2-associated Parkinson's disease.

PURPOSE: Cardiac autonomic dysfunction manifests as reduced heart rate variability (HRV) in idiopathic Parkinson's disease (PD), but no significant reduction has been found in PD patients who carry the LRRK2 mutation. Novel HRV features have not been investigated in these individuals. We aimed to assess cardiac autonomic modulation through standard and novel approaches to HRV analysis in individuals who carry the LRRK2 G2019S mutation. METHODS: Short-term electrocardiograms were recorded in 14 LRRK2-associated PD patients, 25 LRRK2-non-manifesting carriers, 32 related non-carriers, 20 idiopathic PD patients, and 27 healthy controls. HRV measures were compared using regression modeling, controlling for age, sex, mean heart rate, and disease duration. Discriminant analysis highlighted the feature combination that best distinguished LRRK2-associated PD from controls. RESULTS: Beat-to-beat and global HRV measures were significantly increased in LRRK2-associated PD patients compared with controls (e.g., deceleration capacity of heart rate: p = 0.006) and idiopathic PD patients (e.g., 8th standardized moment of the interbeat interval distribution: p = 0.0003), respectively. LRRK2-associated PD patients also showed significantly increased irregularity of heart rate dynamics, as quantified by Rényi entropy, when compared with controls (p = 0.002) and idiopathic PD patients (p = 0.0004). Ordinal pattern statistics permitted the identification of LRRK2-associated PD individuals with 93% sensitivity and 93% specificity. Consistent results were found in a subgroup of LRRK2-non-manifesting carriers when compared with controls. CONCLUSIONS: Increased beat-to-beat HRV in LRRK2 G2019S mutation carriers compared with controls and idiopathic PD patients may indicate augmented cardiac autonomic cholinergic activity, suggesting early impairment of central vagal feedback loops in LRRK2-associated PD.

Investigation of Linear and Nonlinear Properties of a Heartbeat Time Series Using Multiscale Rényi Entropy.

The time series of interbeat intervals of the heart reveals much information about disease and disease progression. An area of intense research has been associated with cardiac autonomic neuropathy (CAN). In this work we have investigated the value of additional information derived from the magnitude, sign and acceleration of the RR intervals. When quantified using an entropy measure, these time series show statistically significant differences between disease classes of Normal, Early CAN and Definite CAN. In addition, pathophysiological characteristics of heartbeat dynamics provide information not only on the change in the system using the first difference but also the magnitude and direction of the change measured by the second difference (acceleration) with respect to sequence length. These additional measures provide disease categories to be discriminated and could prove useful for non-invasive diagnosis and understanding changes in heart rhythm associated with CAN.

Depression and cardiac dysautonomia in eating disorders.

PURPOSE: Individuals with eating disorder (ED) are at an increased risk of cardiac arrhythmias due to cardiac dysautonomia, which may be exacerbated if depression is also present. The aim of the study was to use heart rate analysis as a marker for cardiac dysautonomia in patients with eating disorders and depression as a comorbidity. METHODS: Clinical data, including presence of depression, was obtained from all participants. A three-lead ECG was used to determine interbeat intervals, and these were analyzed using time domain, frequency domain, and nonlinear heart rate variability measures. RESULTS: Thirty ED patients and 44 healthy controls participated in the research. The presence of depression was associated with additional decreased time domain (RMSSD 36.8 ± 26 vs. 22.9 ± 12.3; p < 0.05), frequency domain (HF power 788 ± 1075 vs. 279 ± 261; p < 0.05), and nonlinear domain (DFAα2 0.82 ± 0.1 vs. 0.97 ± 0.1; p < 0.01) which results in the ED group compared to patients with no depression. CONCLUSIONS: The presence of depression in ED patients decreased HRV even further compared to the non-depressed patient group and controls, suggesting that higher vigilance and a holistic treatment approach may be required for these patients to avoid cardiac arrhythmia complications.

Diagnostic Accuracy of Random ECG in Primary Care for Early, Asymptomatic Cardiac Autonomic Neuropathy.

AIMS: Cardiac autonomic reflex tests (CARTs) are time consuming and require patient cooperation for detecting cardiac autonomic neuropathy (CAN). Heart rate variability (HRV) analysis requires less patient cooperation and is quicker to complete. However the reliability of HRV results as a clinical tool, with respect to length of recording and accuracy of diagnosis is inconclusive. The current study investigated the reproducibility associated with varying length of recording for early CAN (eCAN) assessment. METHODS: Participants were 68 males, 72 females with average age of 55 for controls and 63 for early CAN. Inclusion criteria were that participants were medication free and presented with no comorbidities. ECGs of control and eCAN were recorded and heart rate changes analyzed with the fast Fourier transform (FFT) and Lomb-Scargle periodogram (LSP). Ten-second to 5-minute recordings were extracted from a 15-minute lead-II ECG and accuracy in assessment of eCAN determined. RESULTS: The eCAN group was older ( P < .001) and systolic blood pressure was higher ( P < .01). HDL-cholesterol was also higher in the eCAN group ( P < .05). HRV analysis showed that both FFT and LSP results were significantly different between eCAN and control down to a 10-second ECG length for low frequency (LSP: P = .013, FFT: P = .024) and high frequency (HF-LSP: P = .002, FFT: P = .002) power. eCAN assessment was optimal down to 90-second recordings with a sensitivity of 100% and specificity of 29.49%. CONCLUSION: HRV is suitable for clinical practice from ECG recordings of more than 90 seconds with high accuracy and repeatability within a session for each participant.

Socioeconomic status, age and heart rate variability in a Bangladeshi community.

Socioeconomic status (SES) is a risk factor for cardiovascular disease (CVD) and either low or high heart rate variability (HRV) at rest has been shown to predict cardiovascular morbidity and mortality. The study investigated the extent HRV features can predict SES. Four hundred and twenty eight people were randomly selected from the commercial districts (high SES) and slum areas (low SES) within Dhaka city. Demographic, clinical, and HRV features were recorded. Of the clinical variables age, waist circumference and diastolic blood pressure (p<;0.01) were significantly different. HRV feature extraction from heart rate recordings were analyzed using Kubios software. Age corrected results showed that high frequency power (Median (IQR): 112.1 (85.6) ms2 vs. 96.8 (97.6) ms2, p=0.02) and the correlation dimension (0.78 (0.82) vs. 0.51 (1.20), p<;0.0002) were significantly lower in the low SES group, whilst the high frequency peak was significantly higher (0.1500 (0.0004) Hz vs. 0.1503 (0.0066) Hz, p<;0.0001). Our results show that although the high SES group had a more sedentary behavior, the low SES group had a higher risk of cardiac arrhythmia even though they were generally younger with normal blood pressure and waist circumference.

Complex nonlinear autonomic nervous system modulation link cardiac autonomic neuropathy and peripheral vascular disease.

BACKGROUND: Physiological interactions are abundant within, and between, body systems. These interactions may evolve into discrete states during pathophysiological processes resulting from common mechanisms. An association between arterial stenosis, identified by low ankle-brachial pressure index (ABPI) and cardiovascular disease (CVD) as been reported. Whether an association between vascular calcification-characterized by high ABPI and a different pathophysiology-is similarly associated with CVD, has not been established. The current study aims to investigate the association between ABPI, and cardiac rhythm, as an indicator of cardiovascular health and functionality, utilizing heart rate variability (HRV). METHODS AND RESULTS: Two hundred and thirty six patients underwent ABPI assessment. Standard time and frequency domain, and non-linear HRV measures were determined from 5-min electrocardiogram. ABPI data were divided into normal (n = 101), low (n = 67) and high (n = 66) and compared to HRV measures.(DFAα1 and SampEn were significantly different between the low ABPI, high ABPI and control groups (p < 0.05). CONCLUSION: A possible coupling between arterial stenosis and vascular calcification with decreased and increased HRV respectively was observed. Our results suggest a model for interpreting the relationship between vascular pathophysiology and cardiac rhythm. The cardiovascular system may be viewed as a complex system comprising a number of interacting subsystems. These cardiac and vascular subsystems/networks may be coupled and undergo transitions in response to internal or external perturbations. From a clinical perspective, the significantly increased sample entropy compared to the normal ABPI group and the decreased and increased complex correlation properties measured by DFA for the low and high ABPI groups respectively, may be useful indicators that a more holistic treatment approach in line with this more complex clinical picture is required.

How to Calculate Renyi Entropy from Heart Rate Variability, and Why it Matters for Detecting Cardiac Autonomic Neuropathy.

Cardiac autonomic neuropathy (CAN) is a disease that involves nerve damage leading to an abnormal control of heart rate. An open question is to what extent this condition is detectable from heart rate variability (HRV), which provides information only on successive intervals between heart beats, yet is non-invasive and easy to obtain from a three-lead ECG recording. A variety of measures may be extracted from HRV, including time domain, frequency domain, and more complex non-linear measures. Among the latter, Renyi entropy has been proposed as a suitable measure that can be used to discriminate CAN from controls. However, all entropy methods require estimation of probabilities, and there are a number of ways in which this estimation can be made. In this work, we calculate Renyi entropy using several variations of the histogram method and a density method based on sequences of RR intervals. In all, we calculate Renyi entropy using nine methods and compare their effectiveness in separating the different classes of participants. We found that the histogram method using single RR intervals yields an entropy measure that is either incapable of discriminating CAN from controls, or that it provides little information that could not be gained from the SD of the RR intervals. In contrast, probabilities calculated using a density method based on sequences of RR intervals yield an entropy measure that provides good separation between groups of participants and provides information not available from the SD. The main contribution of this work is that different approaches to calculating probability may affect the success of detecting disease. Our results bring new clarity to the methods used to calculate the Renyi entropy in general, and in particular, to the successful detection of CAN.

Cardiac autonomic dysfunction in type 2 diabetes - effect of hyperglycemia and disease duration.

Heart rate variability (HRV) is reduced in diabetes mellitus (DM) patients, suggesting dysfunction of cardiac autonomic regulation and an increased risk for cardiac events. The aim of this paper was to examine the associations of blood glucose level (BGL), glycated hemoglobin (HbA1c), and duration of diabetes with cardiac autonomic regulation assessed by HRV analysis. Resting electrocardiogram (ECG), recorded over 20 min in supine position, and clinical measurements of 189 healthy controls and 93 type 2 DM (T2DM) patients were analyzed. HRV was assessed using several time-domain, frequency-domain, and non-linear methods. HRV parameters showed a clear difference between healthy controls and T2DM patients. Hyperglycemia was associated with increase in mean heart rate and decrease in HRV, indicated by negative correlations of BGL and HbA1c with mean RR interval and most of the HRV parameters. Duration of diabetes was strongly associated with decrease in HRV, the most significant decrease in HRV was found within the first 5-10 years of the disease. In conclusion, elevated blood glucose levels have an unfavorable effect on cardiac autonomic function and this effect is pronounced in long-term T2DM patients. The most significant decrease in HRV related to diabetes and thus presence of autonomic neuropathy was observed within the first 5-10 years of disease progression.

Principal component analysis of heart rate variability data in assessing cardiac autonomic neuropathy.

Heart rate variability (HRV) is recognized to carry early diagnostic value regarding cardiac autonomic neuropathy (CAN). A number of different HRV analysis algorithms have been proposed for the assessment of CAN, each of them providing partly differing information about HRV time series. Instead of confining to a limited set of HRV features, a multi-dimensional approach incorporating a multitude of HRV parameters could be an optimal way of assessing the changes in HRV related to CAN. In this paper, principal component analysis (PCA) is used for analysing multi-dimensional HRV data of 11 patients with definite CAN and 71 subjects without CAN. Using the two most significant principal components, patients with CAN were separated from subjects without CAN with 87% accuracy.

Visualization methods for assisting detection of cardiovascular neuropathy.

Visualization models can assist in understanding the complex pattern of disease, where the signs may be buried in complex data. In this work we propose a new method for visualization of data derived from Heart Rate Variability (HRV) analysis, to indicate whether a person has developed, or is developing, signs of definite Cardiac Autonomic Neuropathy (CAN). Here, the visualizations are compared with actual data recorded from people attending a diabetes clinic with and without definite CAN. Indications from the new visualization technique are compared to the results of established diagnostic measures using the Ewing battery of tests. We find the proposed method to offer useful insights into this disease, as rather than relying upon a binary yes/no decision, it offers a comprehensive picture of the complexity of this disease.

Complexity of heart rate variability in type 2 diabetes - effect of hyperglycemia.

Heart rate variability (HRV) is reduced in diabetes mellitus (DM) patients, suggesting dysfunction of cardiac autonomic regulation which has been associated with increased risk for pathological cardiac events. In this paper, we examined changes in HRV complexity in association to blood glucose level (BGL) and duration of diabetes. Resting HRV and BGL measurements of 32 healthy controls and 54 type 2 DM (T2DM) patients were analyzed. HRV complexity was assessed using Shannon entropy, sample entropy (SampEn), multiscale entropy (MSE), and multiscale Renyi entropy. HRV complexity increased with hyperglycemia indicated by increases in Shannon entropy and MSE and decreases in Renyi entropy for negative orders. Diabetes duration was strongly associated with Renyi entropy which increased for positive orders and decreased for negative orders as a function of disease duration. Shannon entropy, SampEn and MSE did not correlate with disease duration.

Using Renyi entropy to detect early cardiac autonomic neuropathy.

Cardiac Autonomic Neuropathy (CAN) is a disease that involves nerve damage leading to abnormal control of heart rate. CAN affects the correct operation of the heart and in turn leads to associated arrhythmias and heart attack. An open question is to what extent this condition is detectable by the measurement of Heart Rate Variability (HRV). An even more desirable option is to detect CAN in its early, preclinical stage, to improve treatment and outcomes. In previous work we have shown a difference in the Renyi spectrum between participants identified with well-defined CAN and controls. In this work we applied the multi-scale Renyi entropy for identification of early CAN in diabetes patients. Results suggest that Renyi entropy derived from a 20 minute, Lead-II ECG recording, forms a useful contribution to the detection of CAN even in the early stages of the disease. The positive α parameters (1 ≤ α ≤ 5) associated with the Renyi distribution indicated a significant difference (p < 0.00004) between controls and early CAN as well as definite CAN. This is a significant achievement given the simple nature of the information collected, and raises prospects of a simple screening test and improved outcomes of patients.