Jukka A. Lipponen

Kubios HRV - Heart rate variability analysis software

Kubios HRV is an advanced and easy to use software for heart rate variability (HRV) analysis. The software supports several input data formats for electrocardiogram (ECG) data and beat-to-beat RR interval data. It includes an adaptive QRS detection algorithm and tools for artifact correction, trend removal and analysis sample selection. The software computes all the commonly used time-domain and frequency-domain HRV parameters and several nonlinear parameters. There are several adjustable analysis settings through which the analysis methods can be optimized for different data. The ECG derived respiratory frequency is also computed, which is important for reliable interpretation of the analysis results. The analysis results can be saved as an ASCII text file (easy to import into MS Excel or SPSS), Matlab MAT-file, or as a PDF report. The software is easy to use through its compact graphical user interface. The software is available free of charge for Windows and Linux operating systems at http://kubios.uef.fi.

Kubios HRV — A Software for Advanced Heart Rate Variability Analysis

A software for advanced heart rate variability (HRV) analysis is presented. The software includes adaptable tools for correcting artifacts and for removing low frequency trend components. The analysis options of the software include all the commonly used time-domain, frequency-domain and nonlinear HRV parameters. Analysis results can be saved as a PDF report, ASCII text file or Matlab MAT file. The software is easy to use through its compact graphical user interface. Together with a high-quality heart rate monitor, capable of recording beat-to-beat RR intervals, this freely distributed software forms a complete system for HRV analysis.

The effects of VEGF-R1 and VEGF-R2 ligands on angiogenic responses and left ventricular function in mice

AIMS Vascular endothelial growth factors (VEGFs) and their receptors (VEGF-Rs) are among the most powerful factors regulating vascular growth. However, it has remained unknown whether stimulation of VEGF-R1, VEGF-R2 or both of the receptors produces the best angiogenic responses in myocardium. The aim of this study was to compare the VEGF-R1-specific ligand VEGF-B(186), VEGF-R2-specific ligand VEGF-E and VEGF-A(165,) which stimulates both receptors, regarding their effects on angiogenesis and left ventricular function in mice. METHODS AND RESULTS High-resolution echocardiography was used to guide the closed-chest injections of adenoviral (Ad) vectors expressing VEGF-B(186,) VEGF-E, and VEGF-A(165) into the anterior wall of the left ventricle in C57Bl/6J mice. Angiogenic and functional effects were analysed using histology, ultrasound and perfusion analyses 6 (D6) and 14 (D14) days after the Ad injection. AdVEGF-A(165) induced a strong angiogenic response seen as an enlargement of myocardial capillaries whereas angiogenesis induced by AdVEGF-B(186) and AdVEGF-E seemed more physiological. The increase in the capillary area was accompanied with an increase in myocardial perfusion at D6 after the gene injection. AdVEGF-A(165) and AdVEGF-E induced endothelial-specific proliferation whereas AdVEGF-B(186) mostly induced proliferation of cardiomyocytes. AdVEGF-A(165) induced more pronounced tissue damage than AdVEGF-B(186) and AdVEGF-E. Left ventricular function measured as ejection fraction did not change during the follow-up. AdVEGF-A(165) increased both VEGF-R1 and VEGF-R2 protein expression whereas AdVEGF-B(186) and AdVEGF-E did not affect endogenous receptor expression levels. CONCLUSION AdVEGF-B(186) and AdVEGF-E are equally potent in inducing therapeutic angiogenesis in mouse myocardium and produce less side effects than AdVEGF-A(165).

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.

Asynchronicity of facial blood perfusion in migraine.

Asymmetrical changes in blood perfusion and asynchronous blood supply to head tissues likely contribute to migraine pathophysiology. Imaging was widely used in order to understand hemodynamic variations in migraine. However, mapping of blood pulsations in the face of migraineurs has not been performed so far. We used the Blood Pulsation Imaging (BPI) technique, which was recently developed in our group, to establish whether 2D-imaging of blood pulsations parameters can reveal new biomarkers of migraine. BPI characteristics were measured in migraineurs during the attack-free interval and compared to healthy subjects with and without a family history of migraine. We found a novel phenomenon of transverse waves of facial blood perfusion in migraineurs in contrast to healthy subjects who showed synchronous blood delivery to both sides of the face. Moreover, the amplitude of blood pulsations was symmetrically distributed over the face of healthy subjects, but asymmetrically in migraineurs and subjects with a family history of migraine. In the migraine patients we found a remarkable correlation between the side of unilateral headache and the direction of the blood perfusion wave. Our data suggest that migraine is associated with lateralization of blood perfusion and asynchronous blood pulsations in the facial area, which could be due to essential dysfunction of the autonomic vascular control in the face. These findings may further enhance our understanding of migraine pathophysiology and suggest new easily available biomarkers of this pathology.

A Principal Component Regression Approach for Estimation of Ventricular Repolarization Characteristics

The time interval between Q-wave onset and T-wave offset, i.e., QT interval, in an ECG corresponds to the total ventricular activity, including both depolarization and repolarization times. It has been suggested that abnormal QT variability could be a marker of cardiac diseases such as ventricular arrhythmias, and QT-interval has also been observed to lengthen during hypoglycemia. In this paper, we propose a robust method for estimating ventricular repolarization characteristics such as QT interval and T-wave amplitude. The method is based on principal component regression. In the method, QT epochs are first extracted from ECG in respect of R-waves. Then, correlation matrix of the extracted epochs is formed and its eigenvectors computed. The most significant eigenvectors are then fitted to the data to obtain noise-free estimates of QT epochs. Nonstationarities in QT-epoch characteristics can also be modeled by updating the eigenvectors dynamically. The main benefit of the proposed method is robustness to noise, i.e., it works also when using ECGs that have low SNR, for example, signals measured during normal-life environments. One application of the proposed method could be the detection of the hypoglycemia.

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.

Nitroglycerin-induced changes in facial skin temperature: 'cold nose' as a predictor of headache?

Nitroglycerin (NTG) often induces headaches when used to treat cardiac diseases. Such property of NTG has been widely used in modelling of migraine‐like headaches. However, background reasons, predisposing to the development of NTG‐headache, are less studied. The main aim of our study was to find, using NTG model, easily accessible markers of the vascular changes associated with headache. Because changes in the blood flow alter the local skin temperature (Tsk), we studied the relationship between the regional changes in the facial Tsk and NTG‐induced headaches. Tsk was measured with infrared thermography in 11 healthy women during 3 h after sublingual NTG administration. NTG caused headache in five women, and four of them were the first‐degree relatives of migraine patients. Notably, before NTG administration, subjects in the headache group had lower Tsk values, especially in the nose area, than women in the pain‐free group (n = 6). NTG‐induced headache was associated with a long‐lasting increase of Tsk over the baseline. In sharp contrast, in the pain‐free group, the Tsk reduced and returned rapidly to the baseline. Thus, the low baseline level and greater increase of regional Tsk correlated with the incidence of headache that supports a role of greater vascular changes in headache happening on the basis of the dissimilarities in vascular tone. An easily accessible phenomenon of ‘cold nose’ may indicate background vascular dysfunctions in individuals with predisposition to headache. Facial infrared thermography, coupled with NTG administration, suggests a novel temporally controlled approach for non‐invasive investigation of vascular processes accompanying headaches.

Measurements of skin temperature responses to cold exposure of foot and face in healthy individuals: variability and influencing factors.

Skin vasomotor responses to cold exposure (CE) have been measured widely and shown to be abnormal in some clinical conditions. Among other methods, monitoring of skin temperature (Tsk) changes has been applied for those purposes. We investigated such changes simultaneously in different skin areas of healthy young men during foot and facial CE. Tsk was measured using infrared thermography in the big toe and dorsum of the left foot and with a contact thermode in the fingertip. The relationship of Tsk responses within individuals and factors influencing them were examined using mixed model analysis. Tsk changes varied greatly between sessions, measured areas and individuals. Foot CE that was painful produced both stronger central circulatory and Tsk responses than facial CE. Tsk changes were prominent in the fingertip, moderate in the toe and weak or absent in the dorsal foot. The Tsk changes were related to the baseline levels and changes of blood pressure, heart rate, the baseline Tsk values and stimulus intensity. However, despite the different cold stimuli and measurement techniques, an intra‐individual correlation of the Tsk responses was good. In the foot, the big toe area is applicable for studies of Tsk reactions when warm, and the modified Tsk gradient helps to evaluate the level of peripheral vasoconstriction. The cold‐induced Tsk changes may be informative in the studies of the cutaneous vasoregulation but the individual character of the cold stress reactivity and numerous confusing factors should be considered when drawing conclusions on the basis of the recorded results.

Time-varying spectrum estimation of heart rate variability signals with Kalman smoother algorithm

A time-varying parametric spectrum estimation method for analyzing dynamics of heart rate variability (HRV) signals is presented. In the method, HRV signal is first modeled with a time-varying autoregressive model and the model parameters are solved recursively with a Kalman smoother algorithm. Time-varying spectrum estimates are then obtained from the estimated model parameters. The obtained spectrum can be further decomposed into separate components, which is especially advantageous in HRV applications where low frequency (LF) and high frequency (HF) components are generally aimed to be distinguished. As case studies, the dynamics of HRV signals recorded during 1) orthostatic test, 2) exercise test and 3) simulated driving task are analyzed.