Determinants of the heart rate variability in type 1 diabetes mellitus.

Background: Evaluation of heart rate variability (HRV) detects the early subclinical alterations of the autonomic nervous system. Thus, impaired HRV is the earliest subclinical marker of cardiac autonomic neuropathy (CAN) in type 1 diabetes mellitus (T1DM). Objectives: We aimed to explore the HRV parameters in asymptomatic T1DM patients and compare them with the results obtained in healthy subjects. Potential associations between HRV parameters and the established risk factors for CAN and cardiovascular diseases were also investigated. Methods: Seventy T1DM patients (38 ± 12 years, 46 females) and 30 healthy subjects were enrolled into the study. For HRV analysis, beat-to-beat heart rate was recorded for 30 min. The less noisy 5-min segment of the recording was analyzed by Bittium Cardiac Navigator HRV analysis software. Time domain, frequency domain, and nonlinear indices were calculated. Results: Regarding ratio of low to high frequency component (LF/HF), no differences were found between the two populations (p = 0.227). All the further, time domain, frequency domain, and nonlinear HRV indices were significantly lower in T1DM patients (each p < 0.001). In multiple linear models, disease duration remained the only independent predictor of LF/HF ratio (p = 0.019). HbA1c was found to be significant independent predictor of all further time domain (SDNN, p < 0.001; rMSSD, p < 0.001), frequency domain (VLF, p < 0.001; LF, p = 0.002; HF, p = 0.006; Total Power, p = 0.002), and nonlinear indices (SD1, p = 0.006; SD2, p = 0.007), alone, or in combination with other factors, such as age or body mass index. Conclusion: Asymptomatic T1DM patients have significantly reduced overall HRV as compared with healthy subjects, indicating subclinical CAN. Quality of the glycemic control is important determinant of HRV among T1DM patients. This relationship is independent of other risk factors for CAN or cardiovascular diseases.

Aortabillentyu-beültetés antifoszfolipid szindrómában.

Esetismertetés: Egy 44 éves férfi betegnél endokarditisz talaján kialakult súlyos aortabillentyu-elégtelenség tett szükségessé szívsebészeti beavatkozást. A kevesebb mint egy év alatt bekövetkezett többszöri trombotikus esemény felvetette antifoszfolipid szindróma lehetoségét. A lupus antikoaguláns pozitivitás és az említett klinikai kép ezt igazolta. Megbeszélés: Betegünk fiatal életkora és a biológiai mubillentyu korlátozott élettartama ellenére biológiai mubillentyu beültetése mellett döntöttünk. Választásunkat azzal indokoljuk, hogy tanulmányok bizonyítják antifoszfolipid szindrómás betegeknél a mechanikus mubillentyuvel összefüggésbe hozható thromboembolia viszonylag gyakori elofordulását. A mutétet szövodménymentesen elvégeztük, aktivált parciális thromboplastin idovel kontrollált Na-heparin korai adása mellett állítottuk be az orális antikoaguláns terápiát 3,0 INR célértékkel a mutét utáni ötödik napra. A mutét során eltávolított billentyubol korokozó nem tenyészett ki. A kórszövettani vizsgálat abakteriális endokarditiszt véleményezett, nem kizárva a korábbi fertozést. Biológiai mubillentyu implantáció után három hónapig ajánlott aszpirin vagy K-vitamin antagonista adása, betegünk esetében viszont élethosszig tartó antikoaguláns kezelés szükséges, tekintettel rendszerbetegségére. Következtetés: Halmozódó tromboembóliás események kapcsán gondolni kell antifoszfolipid szindrómára, mely igazolása adott esetben meghatározhatja a választható mubillentyu fajtáját. Az ajánlások legtöbbször csak általánosságban fedik le a ritka társbetegségeket, ezért a kapcsolódó szakirodalom áttekintése is szükséges az optimális, betegre szabott döntéshez.

Physical Vascular Therapy (BEMER) Affects Heart Rate Asymmetry in Patients With Coronary Heart Disease.

BACKGROUND/AIM: The aim of this study was to assess the acute effects of physical vascular therapy (PVT) on the autonomous nervous system by heart rate variability (HRV) and heart rate asymmetry (HRA) analysis. The low-frequency, pulsed electromagnetic field (<35 µTesla) with a patented BEMER pattern can improve vasomotion and microcirculation. A non-invasive confirmation of the instant effects of PVT may provide an opportunity to give an immediate feedback to the patient and therapist. PATIENTS AND METHODS: Altogether 48 patients on inward rehabilitation with coronary heart disease (CHD) were involved, their treatment included PVT with B.Box Professional and B.Body Pro applicator (BEMER International AG, Triesen, Lichtenstein). After 15 min of postural adaptation, 6-min electrocardiograms (ECG) were taken immediately before, in the first and in the last 6 min of the 20-min PVT, and one hour after the treatment. Of the 48 patients, the last twenty patients received sham PVT with the same protocol. Off-line analysis was blinded. We used linear mixed statistical model to compare HRV and HRA parameters. RESULTS: The time domain parameters did not show any statistically significant differences between the changes in the real PVT and sham groups but, in the first stage of the treatment, Porta and Guzik indices significantly rose everywhere except in the sham group. CONCLUSION: PVT significantly increases the Guzik and Porta indices in chronic ischemic heart disease patients reflecting a delicate autonomic response. HRA as a measure of autonomic regulation seems to be more sensitive than time domain parameters.

Comment on 'Pulse rate variability in cardiovascular health: a review on its applications and relationship with heart rate variability'.

Precise beat-to-beat fiducial point detection in the photoplethysmogram signal is essential for reliable pulse rate variability (PRV) analysis, which is considered an integral part of health monitoring devices in the evolving era of mobile health. Several studies have aimed to compare PRV to the well-investigated, gold standard heart rate variability (HRV) analysis, to see if they are interchangeable. The agreement between PRV and HRV is not unequivocal, as we learn from the commented metaanalysis. Technical factors like low sampling rate of photoplethysmography (PPG) or imprecise fiducial point detection are more important in this difference than physiological factors corresponding to pulse arrival time. Standardization of the PPG acquisition and reference point detection is necessary for comparable studies and correct measurement.

Cardiac resynchronization therapy with intraoperative epicardial mapping via minithoracotomy: 10 years' experience.

BACKGROUND: Cardiac resynchronization therapy (CRT) is considered an efficient method to improve the left ventricular (LV) dysfunction with left bundle branch block. However, coronary venous anatomy is not appropriate in about 10% of the cases; thus other alternatives, such as epicardial lead implantation via minithoracotomy are needed. METHODS: During the period 2007-2017, a total of 57 patients were operated at our institute via left anterior minithoracotomy after an unsuccessful transvenous CRT. The best position of the LV epicardial electrode was determined by intraoperative epicardial mapping, that is locating the latest activation spot relative to the right ventricular (RV) electrode. The authors analyzed the survival by Kaplan-Meier estimator with Tarone-Ware equality test and multiple Cox regression analysis, the changes of the LV ejection fraction (LVEF) and dimensions, the development of the impedance and threshold of the LV epicardial electrode, the possible associations between the survival and intraoperative sensed RV-LV activation delay. RESULTS: The intraoperative RV-LV activation delay was 92.250 ± 26.538 milliseconds. There were no intraoperative complications except ventricular fibrillation in three patients. Within 30 days there were neither wound healing complications nor pocket hematoma. There was no significant difference in survival with regard to gender or etiology, but significantly better survival was found in the cohort with intraoperative sensed RV-LV activation delay >86 milliseconds. The LVEF and dimensions improved following the operation and continued to be improved in the survivors. CONCLUSION: CRT via minithoracotomy with epicardial mapping is a safe, efficient, simple, and reproducible second-line alternative to the transvenous method.

Cellular Phone Irradiation of the Head Affects Heart Rate Variability Depending on Inspiration/Expiration Ratio.

BACKGROUND: Mobile phones may have harmful health effects and clinical examinations report ambiguous results of exposure concerning neurophysiological and cardiovascular actions. MATERIALS AND METHODS: This study investigated heart rate asymmetry (HRA) and heart rate variability (HRV) parameters with 1:2 and 1:1 metronome-paced inspiration/expiration ratios during short-term 1,800MHz GSM cellular phone exposure in 20 healthy volunteers. RESULTS: Significant HRA changes by Porta and Guzik indices were not found on exposure compared to sham exposure. Time-domain HRV parameters on exposure showed significant differences at 1:1 paced, but not at 1:2 paced breathing compared to sham exposure. A mild post-exposure effect was observed regarding root mean square of successive RR-differences. CONCLUSION: The findings reflect persisting acute effects of GSM handset emission on the autonomic nervous system. Exploring its influences on health status and survival needs further studies. Symmetrical breathing can be used as a sensitizing factor in other HRV/HRA analysis studies.

Transcutaneous Carbon Dioxide Treatment Affects Heart Rate Variability - A Pilot Study.

BACKGROUND: The aim of this study was to investigate the effects of carbon-dioxide treatment on heart rate variability (HRV) parameters: mean RR interval (RRI), standard deviation of RR intervals (SDNN), root mean square of successive RR differences (RMSSD); and Porta and Guzik indices, as measures of heart rate asymmetry. MATERIALS AND METHODS: Twenty patients were enrolled (mean±SD, age=59±7.8 years). Measurements were performed before CO2 treatment, at the beginning of treatment, at 15 min of treatment, immediately after and 1 h after the treatment. RESULTS: Significant increase in SDNN was found 1 h after the treatment when compared to that before it (p=0.011). There were no significant changes in other parameters. CONCLUSION: CO2 treatment can influence the autonomic nervous system identified by SDNN changes. However, larger studies are required to confirm these results.

[Perioperative use of levosimendan in cardiac surgery. Hungarian recommendation]. / A levoszimendán perioperatív alkalmazása a szívsebészetben. Magyar ajánlás.

Low output syndrome significantly increases morbidity and mortality of cardiac surgery and lengthens the durations of intensive care unit and hospital stays. Its treatment by catecholamines can lead to undesirable systemic and cardiac complications. Levosimendan is a calcium sensitiser and adenosine triphosphate (ATP)-sensitive potassium channel (IK,ATP) opener agent. Due to these effects, it improves myocardium performance, does not influence adversely the balance between O2 supply and demand, and possesses cardioprotective and organ protective properties as well. Based on the scientific literature and experts' opinions, a European recommendation was published on the perioperative use of levosimendan in cardiac surgery in 2015. Along this line, and also taking into consideration cardiac surgeon, anaesthesiologist and cardiologist representatives of the seven Hungarian heart centres and the children heart centre, the Hungarian recommendation has been formulated that is based on two pillars: literature evidence and Hungarian expert opinions. The reviewed fields are: coronary and valvular surgery, assist device implantation, heart transplantation both in adult and pediatric cardiologic practice. Orv Hetil. 2018; 159(22): 870-877.

Comment on 'Photoplethysmography sampling frequency: pilot assessment of how low can we go to analyze pulse rate variability with reliability?'

Accurate pulse rate detection is essential for reliable pulse rate variability analysis. On the other hand, minimizing the sampling frequency is essential to reduce the amount of data and computational needs, and consequently the power consumption of mobile/wearable devices, extending their operating hours. Determining the variability of physiological parameters needs a new paradigm since there is a limited possibility of calculating an average eliminating random error of measurement. Finding the optimal sampling rate depends on the actual investigation, the expected variability and variability-changes of the study-population in order to get valid HRV parameters.

The issue of plasma asymmetric dimethylarginine reference range - A systematic review and meta-analysis.

BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase, marker and mediator of endothelial dysfunction. Several studies have demonstrated its value in cardiovascular risk stratification and all-cause mortality prediction. The aim was to determine the reference range of plasma ADMA in healthy adults. METHODS AND RESULTS: Taking into account the most widely used ADMA measurement methods, only studies using either high performance liquid chromatography (HPLC) -with fluorescence or mass spectrometric detection-, or enzyme-linked immunosorbent assay (ELISA) to quantify plasma ADMA concentrations were enrolled. 66 studies were included in the quantitative analysis (24 using ELISA and 42 using HPLC) reporting a total number of 5528 non-diabetic, non-hypertensive, non-obese adults without any medication (3178 men and 2350 women, 41.6 ± 16.9 years old). The reference range of ADMA (in µmol/l with 95% confidence interval in parenthesis) was 0.34 (0.29-0.38)- 1.10 (0.85-1.35) with a mean of 0.71 (0.57-0.85) (n = 4093) measured by HPLC and 0.25 (0.18-0.31)- 0.92 (0.76-1.09) with a mean of 0.57 (0.48-0.66) (n = 1435) by ELISA. CONCLUSIONS: Numerous publications suggested that asymmetric dimethylarginine is not only an outstanding tool of disease outcome prediction but also a new potential therapeutic target substance; the reference range provided by this meta-analysis can become of great importance and aid to further investigations. However, developing a standard measurement method would be beneficial to facilitate the clinical usage of ADMA.

Pain-related autonomic response is modulated by the medial prefrontal cortex: An ECG-fMRI study in men.

BACKGROUND: Our goal was to identify brain structures responsible for pain-related autonomic changes by the correlation of simultaneously acquired functional magnetic resonance imaging (fMRI) and electrocardiogram (ECG) data. METHODS: Eighteen healthy men (age: 22.89 ± 1.96) were involved. Painful sensation was evoked by heat. Simultaneously recorded brain fMRI and ECG data during pain were compared to data acquired during a non-painful heat sensation. From the ECG data, time- and frequency domain parameters of heart rate variability (HRV) were extracted. RESULTS: We found that: (1) among the common elements of both pain network and central autonomic network (CAN) only the medial prefrontal frontal cortex (MPFC) showed significant correlation with HRV; (2) the parasympathetic response to the painful stimuli showed a positive, while the sympathetic response a negative association with pain related BOLD-signal change observed in MPFC; (3) time domain parameters of HRV were negatively associated with MPFC activation. CONCLUSIONS: The novelty of our study-compared to previous ECG-fMRI studies-is that we used pain as stimulus and investigated both frequency- and time-domain parameters of HRV. Compared to other stimuli used in earlier studies to activate the CAN, pain sensation can be standardized easier and might allow us to better understand the functional organization of CAN. The results of the current ECG-fMRI study may have direct clinical relevance in understanding the pathomechanisms of several clinical conditions. PERSPECTIVE: There are some simultaneous ECG-fMRI and ECG-Positron Emission Tomography (PET) studies, but limited information is available about the pain-related brain function-HRV relations. The novelty of our study is that we used pain as stimulus to activate the central autonomic network and investigated both frequency- and time-domain parameters of HRV.

Selecting the optimal anti-aliasing filter for multichannel biosignal acquisition intended for inter-signal phase shift analysis.

The availability of microcomputer-based portable devices facilitates the high-volume multichannel biosignal acquisition and the analysis of their instantaneous oscillations and inter-signal temporal correlations. These new, non-invasively obtained parameters can have considerable prognostic or diagnostic roles. The present study investigates the inherent signal delay of the obligatory anti-aliasing filters. One cycle of each of the 8 electrocardiogram (ECG) and 4 photoplethysmogram signals from healthy volunteers or artificially synthesised series were passed through 100-80-60-40-20 Hz 2-4-6-8th order Bessel and Butterworth filters digitally synthesized by bilinear transformation, that resulted in a negligible error in signal delay compared to the mathematical model of the impulse- and step responses of the filters. The investigated filters have as diverse a signal delay as 2-46 ms depending on the filter parameters and the signal slew rate, which is difficult to predict in biological systems and thus difficult to compensate for. Its magnitude can be comparable to the examined phase shifts, deteriorating the accuracy of the measurement. As a conclusion, identical or very similar anti-aliasing filters with lower orders and higher corner frequencies, oversampling, and digital low pass filtering are recommended for biosignal acquisition intended for inter-signal phase shift analysis.

Effects of spinal cord stimulation on heart rate variability in patients with chronic pain.

BACKGROUND: Spinal cord stimulation has become an established clinical option for treatment of refractory chronic pain and angina pectoris, but its precise mechanism of action is unclear. We investigated the effect of spinal cord stimulation (SCS) on heart rate variability (HRV) and evaluating its influence on the sympathetic/parasympathetic balance in chronic pain. MATERIALS AND PURPOSE: Seven patients (three men, four women) with SCS due to chronic pain were included. The SCS was programmed in three different ways: (i) to stimulate at an amplitude known to generate paresthesias (ON-state), (ii) at a subliminal level (SUB state), or (iii) switched off (OFF-state). HRV analysis was based on 5-min segments of the consecutive normal RR intervals and was performed with custom software (Kubios HRV Analysis). RESULTS: The mean heart rate was higher in ON state compared to SUB state (p = 0.018) and the high-frequency component of the HRV was lower in ON compared to OFF period (p = 0.043). Other HRV parameters values did not significantly differ during the three tested periods. CONCLUSION: Spinal cord stimulation in chronic pain seems to be accompanied by reduced parasympathetic tone, unlike SCS in angina pectoris where previous studies found a reduced cardiac sympathetic tone. Our study might lead to understand the mechanism of action of SCS We investigated a relatively small number of patients, which is the main limitation of our study. Thus, further studies with larger number of patients are required for validation of our results.

The assessment of neural injury following open heart surgery by physiological tremor analysis.

INTRODUCTION: The appearance of post-operative cognitive dysfunction as a result of open heart surgery has been proven by several studies. Focal and/or sporadic neuron damage emerging in the central nervous system may not only appear as cognitive dysfunction, but might strongly influence features of physiological tremor. MATERIAL AND METHODS: We investigated 110 patients (age: 34-73 years; 76 male, 34 female; 51 coronary artery bypass grafting (CABG), 25 valve replacement, 25 combined open heart surgery, 9 off-pump CABG) before surgery and after open-heart surgery on the 3(rd) to 5(th) post-operative day. The assessment of the physiological tremor analysis was performed with our newly developed equipment based on the Analog Devices ADXL 320 JPC integrated accelerometer chip. Recordings were stored on a PC and spectral analysis was performed by fast Fourier transformation (FFT). We compared power integrals in the 1-4 Hz, 4-8 Hz and 8-12 Hz frequency ranges and these were statistically assessed by the Wilcoxon rank correlation test. RESULTS: We found significant changes in the power spectrum of physiological tremor. The spectrum in the 8-12 Hz range (neuronal oscillation) decreased and a shift was recognised to the lower spectrum (p < 0.01). The magnitude of the shift was not significantly higher for females than for males (p < 0.157). We found no significant difference between the shift and the cross-clamp or perfusion time (p < 0.6450). CONCLUSIONS: The assessment of physiological tremor by means of our novel, feasible method may provide a deeper insight into the mechanism of central nervous system damage associated with open heart surgery.

Heart rate asymmetry follows the inspiration/expiration ratio in healthy volunteers.

Heart rate asymmetry (HRA) quantifies the uneven distribution of points above and below the identity-line in a Poincaré plot of RR-intervals. The authors investigated if HRA could be influenced by the inspiration/expiration ratio. Healthy volunteers (n = 18) were studied in the supine position at 4.5 s metronome breathing. ECG and breathing signals were recorded for 360 s at each breathing pattern: inspiration controlled, inspiration/expiration controlled (1:2, 1:1, 2:1 ratio), inspiration controlled again. Time domain, frequency domain and Poincaré plot heart rate variability (HRV) analysis with Porta's and Guzik's indices were performed on 300 s tachograms. There were no statistically significant differences in time domain, frequency domain and standard Poincaré plot parameters during the various breathing patterns, whereas Porta's and Guzik's indices significantly rose at 1:1 and 2:1 compared to physiological 1:2 breathing. There were no significant differences in the HRA parameters between the first and the last runs. In our population the inspiration/expiration ratio significantly influenced HRA, but not standard HRV parameters. Positive correlation of Guzik's and Porta's index reflects reciprocal changes of the number of points and their dispersion in the accelerating and decelerating sets of RR-intervals. HRA-analysis can be a promising method for investigating cardiovascular regulation/health particularly with further spreading of wearable monitors.

Pharmacotechnological pitfalls of priming--possible source of microembolization during open heart surgery.

OBJECTIVES: Besides low mortality and morbidity rates in cardiac surgery, the associated cognitive dysfunction is the focus of interest. One possible reason is microembolisation. METHODS AND RESULTS: The authors analysed the crystallogenesis in the calcium-containing prime, inspired by their observation that the fluid sometimes becomes turbid during the priming process. Lactated Ringer-based prime solutions were tested, adding mannitol, NaHCO(3), and heparin. The oxygenator was ventilated with compressed medical air. Samples were taken for dynamic light scattering particulate level analysis. The priming was furthermore modelled in the laboratory by mixing the components and then ventilating the mixture through with compressed air. Turbid solutions from the operating room contained 100-6500 nm crystals, while clear solutions contained 20-473 nm particles. In the model, continuous pH measurement showed pH 6.4-7.4 after blending the solutions, which then elevated the pH to 7.5-8.0 after ventilation with concomitant turbidity. The pH of the prime can be stabilized by the addition of ascorbic acid (1-2 mg/ml) and, also, the turbidity may be prevented. CONCLUSION: Ventilating the lactated Ringer-based calcium-containing primes after blending is not advisible because of alkalization and crystallogenesis. Ascorbic acid stabilizes the pH and prevents crystallogenesis in the prime. Pre-bypass filtration is recommended.

Simple and choice reaction times are prolonged following extracorporeal circulation: a potential method for the assessment of acute neurocognitive deficit.

BACKGROUND: Cognitive deficit related to open heart surgery came into the focus of interest according to professional and social expectations. The negative effects on quality of life and the large number of involved patients emphasize the need its investigation. MATERIAL/METHODS: The bedside measurement of simple and choice reaction times (sRT and cRT) has the objectivity of cortical evoked potential analysis without the need for EEG instrumentation and laboratory. This is a functional assessment similar to neuropsychological tests, but requires a significantly shorter time and is less demanding for the patient. RESULTS: Fifty patients who had undergone open heart surgery were investigated. Statistically significant positive correlation of sRT and cRT prolongation and perfusion time was found. At the same time there were no statistically significant changes in mean sRT and cRT values before (sRT: 208+/-54 s, cRT: 369+/-59 s) and after (sRT: 229+/-67 s, cRT: 392+/-105 s) the surgery, probably due to the inhomogeneous patient population. The weak correlation (coefficients: 0.1418-0.8484) for sRT and cRT changes as a function of perfusion time confirms the presence of other factors of postoperative brain damage. CONCLUSIONS: The investigated bedside test is clinically feasible, simple, and can be completed within 30 minutes. Further studies are encouraged to compare this method with other tests in a larger, stratified cardiac surgery population.

[Effect of epileptic seizures on the heart rate]. / Az epilepsziás rohamok hatása a szívfrekvenciára.

BACKGROUND: Sudden death appears in 8-17% of epilepsy patients non-responding to antiepileptic therapy. Some studies suggest that the most common cause of death is seizure-related cardiac arrhythmia. AIM OF STUDY: To analyze the alteration of the heart rate six hours before and after the seizures. METHODS: Eighteen patients suffering from focal epilepsy were examined before epilepsy surgery. Video-EEG-ECG was carried out for 2-10 days, and 32 seizures were registered. Analysis of the heart rate was based on the 5-minute-long epochs of the ECGs taken at the 5-10-15-30th minutes and at the 1-3-6th hours before and after seizures. RESULTS: The heart rate increases (from an average of 69 beats/min to 92 beats/min, p<0.001) immediately after seizures, though significantly higher heart rate was observed 3 hours after seizures. There were no patients with severe peri-ictal bradycardia. In one of our patients, ectopic cardiac rhythm occurred after a generalized tonic-clonic seizure. CONCLUSIONS: We can conclude that the sympathetic activity increases while the parasympathetic activity decreases after seizures. The observed alterations lasted for a long time and predict fatal arrhythmias. These suggest that sudden death in epilepsy can be induced by cardiac arrhythmias connected with epileptic seizures.

[Pumpless extracorporeal lung assist]. / A minimalizált extracorporális tüdôtámogatás.

The recently introduced pumpless extracorporeal lung assist (PECLA) is a remarkable alternative to the conventional extracorporeal membrane oxygenation in case of severe lung failure. By establishing a shunt between femoral artery and vein using the arterio-venous pressure gradient as a driving force through a low-resistance membrane oxygenator, PECLA provides highly effective gas-exchange by preserved cardiac function. Due to its closed system, reduced priming volume and low heparin demand, the unfavourable effects of extracorporeal membrane oxygenation can be effectively diminished. Hence the small technical, financial and personal input, the PECLA can be ideally used in district hospitals and during transport as well. Our short summary demonstrates the advantages and safety of the system proven over 123 cases.