A combined computational and experimental approach to assess the transfer function of real pacemaker leads for MR radiofrequency-induced heating.

OBJECTIVE: To propose and validate a variation of the classic techniques for the estimation of the transfer function (TF) of a real pacemaker (PM) lead. METHODS: The TF of three commercially available PM leads was measured by combining data from experimental measurements and numerical simulations generated by three sources: a) the experimental local SAR at the tip of the PM lead (single measurement point) exposed to a 64 MHz birdcage body coil; b) the experimental current distribution along the PM lead, obtained by directly injecting a 64 MHz signal inside the lead; c) the electric field (E-field) simulated with a computational model of the 64 MHz birdcage body coil adopted in the experimental measurement performed in a). The effect of the lead trajectory on the estimation of the TF was also estimated. RESULTS: The proposed methodology was validated by comparing the SAR obtained from the PM lead TF with experimental measurements: a maximum difference of 2.2 dB was observed. It was also shown that the estimation of the TF cannot be considered independent with the lead trajectory: a variation of the SAR estimation up to 3.4 dB was observed. CONCLUSION: For the three PM lead tested, the error in the SAR estimation is within the uncertainty level of SAR measurements (± 2 dB). Additionally, the estimation of the TF using the reciprocity principle is influenced by the particular lead trajectory adopted, even if the consequent variability in the SAR estimation is still close to the uncertainty level of SAR measurements.

Autonomic cardiovascular function and baroreflex sensitivity in patients with cervical dystonia receiving treatment with botulinum toxin type A.

OBJECTIVE: To investigate possible changes in autonomic cardiovascular regulation and cardiopulmonary baroreflex sensitivity in patients with primary cervical dystonia receiving chronic treatment with botulinum toxin type A. METHODS: Short-term power spectral analysis of heart rate and systolic blood pressure variability, high-frequency and low-frequency oscillations of heart rate variability, low frequency/high frequency ratio and baroreflex sensitivity (alpha index) were measured in 12 patients with cervical dystonia before and 2-4 weeks after botulinum toxin type A injection and compared with normative data. RESULTS: Before treatment, at rest, patients had significantly lower high frequency power than healthy subjects (p < 0.01), whereas no differences were found in low frequency power. Botulinum toxin injection in patients induced no changes in either power frequency. In patients before treatment and healthy subjects the low frequency oscillatory components increased similarly from rest to tilt (p < 0.01), but tilt induced lower low frequency values in patients than in healthy subjects (p < 0.01). In patients before treatment, the high frequency variations from rest to tilt remained unchanged, whereas in healthy subjects they decreased significantly (p < 0.01). Botulinum toxin type A injection in patients induced no changes in low frequency or high frequency powers. In patients before treatment the low frequency/high frequency ratio increased slightly from rest to tilt, but in healthy subjects increased significantly (p < 0.01). Botulinum toxin type A left the pretreatment low frequency/high frequency ratio unchanged. The alpha-index measured at rest in patients before treatment was lower than in healthy subjects (p<0.05), whereas during tilt was similar in both groups. The alpha-index measured after botulinum toxin injection in patients remained unchanged at rest and during tilt. CONCLUSIONS: Patients with cervical dystonia receiving treatment with botulinum toxin type A have mild, subclinical abnormalities in autonomic cardiovascular regulation and cardiopulmonary baroreflex sensitivity. These changes do not worsen after acute botulinum toxin type A injection.

Temperature and SAR measurement errors in the evaluation of metallic linear structures heating during MRI using fluoroptic probes.

The purpose of this work is to evaluate the error associated with temperature and SAR measurements using fluoroptic temperature probes on pacemaker (PM) leads during magnetic resonance imaging (MRI). We performed temperature measurements on pacemaker leads, excited with a 25, 64, and 128 MHz current. The PM lead tip heating was measured with a fluoroptic thermometer (Luxtron, Model 3100, USA). Different contact configurations between the pigmented portion of the temperature probe and the PM lead tip were investigated to find the contact position minimizing the temperature and SAR underestimation. A computer model was used to estimate the error made by fluoroptic probes in temperature and SAR measurement. The transversal contact of the pigmented portion of the temperature probe and the PM lead tip minimizes the underestimation for temperature and SAR. This contact position also has the lowest temperature and SAR error. For other contact positions, the maximum temperature error can be as high as -45%, whereas the maximum SAR error can be as high as -54%. MRI heating evaluations with temperature probes should use a contact position minimizing the maximum error, need to be accompanied by a thorough uncertainty budget and the temperature and SAR errors should be specified.

P-wave morphology assessment by a gaussian functions-based model in atrial fibrillation patients.

Aim of this study was to present a P-wave model, based on a linear combination of Gaussian functions, to quantify morphological aspects of P-wave in patients prone to atrial fibrillation (AF). Five-minute ECG recordings were performed in 25 patients with permanent dual chamber pacemakers. Patients were divided into high-risk and low-risk groups, including patients with and without AF episodes in the last 6 mo preceding the study, respectively. ECG signals were acquired using a 32-lead mapping system for high-resolution biopotential measurement (ActiveTwo, Biosemi, The Netherlands, sample frequency 2 kHz, 24-bit resolution). Up to 8 Gaussian models have been computed for each averaged P-wave extracted from every lead. The P-wave morphology was evaluated by extracting seven parameters. Classical time-domain parameters, based on P-wave duration estimation, have been also estimated. We found that the P-wave morphology can be effectively modeled by a linear combination of Gaussian functions. In addition, the combination of time-domain and morphological parameters extracted from the Gaussian function-based model of the P-wave improves the identification of patients having different risks of developing AF.

Pacemaker and ICD oversensing induced by movements near the MRI scanner bore.

PURPOSE: The effect of the movement near the MRI scanner bore for people with a pacemaker (PM) or an implantable cardioverter defibrillator (ICD) is experimentally evaluated and discussed. METHODS: The authors performed in vitro measurements on a saline-filled human-shaped phantom (male, 170 cm height), equipped first with an MR-conditional PM (bicameral configuration, DDD programming), then with an MR-conditional ICD (biventricular configuration, detection algorithms enable but shock delivery disable). Both the devices were able to transmit in real-time the detected cardiac activity (electrograms) while moving the phantom around the MRI scanner. The phantom was also equipped with an accelerometer and a magnetic field probe to measure the angular velocity and the magnetic field variation during the experiment. Unipolar versus bipolar sensing mode and maximum sensitivity versus nominal settings were tested. RESULTS: The sensing functions of the PM and ICD systems began to react to motion induced electromagnetic interference starting at an angular velocity as low as 2 rad/s (|dB/dT| = 2 T/s). The motion induced EMI in PM and ICD systems was interpreted as sensed intrinsic heartbeats which resulted in inappropriate pacing inhibition and arrhythmia classification. At the maximum speed of about 6 rad/s (|dB/dT| = 3 T/s), the induced EMI affected classification of ectopic beats and two episodes of VF were inappropriately recorded. CONCLUSIONS: These results demonstrate that motion in and around an MR scanner can induce EMI significant enough to be misinterpreted by implanted PMs and ICDs leading to inappropriate changes in therapy. These findings highlight that PM or ICDs, including MR-conditional systems should not enter the MRI room, except in case of an examination under specified conditions.

A telemonitoring platform for the investigation of blood pressure profiles in pacemaker patients.

Rate responsive pacemakers (PM) use different strategies to adapt the patient paced rate, with the aim of having the best hemodynamic performance in response to internal or external conditions. Closed-loop stimulation (CLS) uses intracardiac impedance as a sensor principle. The evaluation of impact of different pacing modalities and technologies on the blood pressure (BP) profiles is mainly investigated in short-term laboratory settings, mainly due to the need of reliable daily-based BP values. The impact of CLS pacing on systemic blood pressure (BP) has been studied on short term basis, but data on long term effects are scarse. This study present a telemedicine platform designed for evaluating the effect of the rate responsive technology on daily systolic and diastolic BP data. BP and pacemaker data were collected daily from fourteen patients during a 3 month period. The total number of monitoring days was 1277 (91 day/patient), for a total number of 4455 BP measures. On average 3.5 measure/day/patient were received). The analysis of the BP data showed that CLS pacing results in diastolic pressure closer to the normal values than accelerometer-based pacing, which were associated to lower diastolic pressures.

Effects of sleep stage and age on short-term heart rate variability during sleep in healthy infants and children.

STUDY DESIGN: Power spectrum analysis of heart rate variability (HRV) is a noninvasive technique that provides a quantitative assessment of cardiovascular neural control. Using this technique, we studied the autonomic nervous system changes induced by sleep in 14 healthy subjects: 7 infants (mean age, 9.40 +/- 2.32 months) and 7 children (mean age, 8.93 +/- 0.65 years) during a standard all-night polysomnographic recording. Our primary aim was to assess the effect of sleep stage and age on short-term HRV during sleep in healthy infants and children. Power spectral density was estimated by autoregressive modeling over 250 consecutive R-R intervals. In this study, we mainly considered two spectral components: the high-frequency (HF) component (0.15 to 0.40 Hz), which reflects parasympathetic cardiovascular modulation; and the low-frequency (LF) component (0.04 to 0.15 Hz), generally considered due to both parasympathetic and sympathetic modulation. RESULTS: Heart rate was higher (p < 0.01 in all sleep stages) and total power lower (p < 0. 02) in infants than in children. HF power was higher in children than in infants (p < 0.05). In infants and children, the ratio between LF and HF powers changed with the various sleep stages (p < 0.02 in infants; p < 0.01 in children): it decreased during deep sleep and increased during rapid eye movement sleep. However, it was invariably lower in children than in infants. CONCLUSION: These findings show that the sleep stage and age both significantly influence short-term HRV during sleep in healthy infants and children. Hence, to provide unbiased results, HRV studies investigating the effects of age on autonomic nervous system activity should segment sleep into the five stages. In addition, despite a relatively small study sample, our data confirm greater parasympathetic control during sleep in children than in infants.

Respiratory sinus arrhythmia and cardiovascular neural regulation in athletes.

Studies using spectral analysis of cardiovascular variability as a noninvasive means for assessing autonomic nervous system activity have provided controversial results in athletes. One reason is that a slow breathing rate--a common feature in athletes--affects spectral estimation because it causes the low-frequency (LF) and high-frequency (HF) components to overlap. Low-frequency power increases during sympathetic activation; high-frequency corresponds to respiratory sinus arrhythmia. In this study, to assess how controlled respiration influences autonomic nervous system activity, we determined the effect of controlled and uncontrolled breathing conditions on cardiovascular variability. Our aim was to identify a standard respiratory rate for spectral estimation of cardiovascular neural control in athletes. During electrocardiographic recordings, subjects lay supine and breathed at their spontaneous frequency and at rates of 15, 12, and 10 to 14 (random) breaths x min(-1). Uncontrolled and random breathing rates significantly altered spectral sympathetic indices; conversely, 15 and 12 breaths x min(-1) redistributed respiratory related power through the HF, thus yielding correct LF power estimation. None of the breathing conditions significantly changed mean heart rate, arterial blood pressure, or spectral total power of cardiovascular variability. In conclusion, when power spectral analysis is used for assessing autonomic activity in athletes, respiration should be standardized at 15 breaths x min(-1). Controlled respiration at this rate leaves autonomic nervous system activity unchanged.

On the mechanisms of interference between mobile phones and pacemakers: parasitic demodulation of GSM signal by the sensing amplifier.

The aim of this study was to investigate the mechanisms by which the radiated radiofrequency (RF) GSM (global system for mobile communication) signal may affect pacemaker (PM) function. We measured the signal at the output of the sensing amplifier of PMs with various configurations of low-pass filters. We used three versions of the same PM model: one with a block capacitor which short circuits high-frequency signals; one with a ceramic feedthrough capacitor, a hermetically sealed mechanism connecting the internal electronics to the external connection block, and one with both. The PMs had been modified to have an electrical shielded connection to the output of the sensing amplifier. For each PM, the output of the sensing amplifier was monitored under exposure to modulated and non-modulated RF signals, and to GSM signals (900 and 1800 MHz). Non-modulated RF signals did not alter the response of the PM sensing amplifier. Modulated RF signals showed that the block capacitor did not succeed in short circuiting the RF signal, which is somehow demodulated by the PM internal non-linear circuit elements. Such a demodulation phenomenon poses a critical problem because digital cellular phones use extremely low-frequency modulation (as low as 2 Hz). which can be mistaken for normal heartbeat.

Comparing the effects of nasal synchronized intermittent positive pressure ventilation (nSIPPV) and nasal continuous positive airway pressure (nCPAP) after extubation in very low birth weight infants.

In this study we hypothesized that nasal synchronized intermittent positive pressure ventilation (nSIPPV) would provide more ventilatory support than nasal continuous positive airway pressure (nCPAP) in the immediate post-extubation period in very low birth weight (VLBW) infants. We tested this hypothesis by comparing the effects of these two ventilatory techniques on ventilation, gas exchange, and patient inspiratory effort in 11 preterm infants immediately after extubation. All neonates studied (BW: 1141+/-(SEM) 53 g; GA: 28.1+/-(SEM) 0.5 wks) had received mechanical ventilation because of respiratory distress at birth and were extubated by day 14 of life. Nasal SIPPV and nCPAP were applied in random order to each infant after extubation so that each was his/her own control. Both nCPAP and nSIPPV were delivered at end-expiratory pressures (PEEP) of 3 cm H2O. Inspiratory times (Ti) and peak inspiratory pressures set during nSIPPV were the same as those used at the time of extubation. Recordings lasted 45 min in each mode of ventilation. Tidal volume (Vt), minute volume (Ve), respiratory rate (RR), airway pressure (Paw), transcutaneous PO2 (TcPO2) and PCO2 (TcPCO2) as well as phasic esophageal pressure deflections (Pe), as an estimate of inspiratory effort, were measured. The measurements obtained during both modes of ventilation indicated significant differences between the two techniques. Indeed, application of nSIPPV was associated with a statistically significant increase in Vt and Ve. In addition, Pe decreased by 30% during nSIPPV (P<0.01). TcPCO2 was statistically significantly lower during nSIPPV than nCPAP, and RR as well. These data therefore suggest that nSIPPV may provide more ventilatory support than nCPAP in the post-extubation period with less patient inspiratory effort.

Fully automated ambulatory blood pressure in the diagnosis and therapy of hypertension.

Technical characteristics of a fully automatic apparatus for ambulatory semicontinuous blood pressure monitoring are described. Initially, we ascertained the reliability and the fidelity in the reproduction of studied events (blood pressure, heart rate, ECG). Good results were obtained, even in comparison with other methods (blood pressure semiautomatic or invasive monitoring). We then studied the results of the research on 200 hypertensive subjects. The easy applicability of this method allowed us to demonstrate blood pressure variability over a 24-h patient period. We now can evaluate the factors contributing to blood pressure variability and the alterations contributing to the meaning of circadian rhythm. We are now able to comment on the prevalent incidence of organic or neurogenic components in single hypertensive states, the possible coexistence of asymptomatic coronary heart disease, and on the choice and efficacy of hypotensive drugs.

Spontaneous fluctuations of human pupil reflect central autonomic rhythms.

Aim of this study is to assess whether and to what extent LF and HF rhythms contribute to spontaneous pupil diameter fluctuations at rest and during sympathetic activation by Head-Up Tilt Test 70 degrees. ECG, Finapres and Respiration data from 10 normal subjects were recorded simultaneously to spontaneous pupil diameter fluctuations (SPDF). The respiratory rhythm and the LF component were clearly detected in all the SPDF series. The cross-spectrum analysis gave significant results (> 0.5) in HF band. During tilt, a reduction in the total variability with a relative increase of the LF component was observed in HR, BP and SPDF signals. The multivariate analysis of the SPDF and of the cardiovascular variability series allows new insights into the physiology of pupil neural control. The effect of tilting on SPDF spectra and the physiological background of the pupil control are consistent with the hypothesis that pupil fluctuations reflect a generalized increase of the sympathetic tone.

Effects of subthreshold shocks on wavelet propagation during atrial fibrillation in humans.

OBJECTIVES: Our objectives are: first to investigate the effects of internal cardioversion energies on the wave fronts propagation in the right atrium immediately after the energy delivery; second, to track the time course of these effects. METHODS: The study is based on a measure of organization of the endoatrial electrograms obtained by a multipolar basket catheter inserted in the right atrium. We estimated the level of organization by computing the percentage of points laying on the signal baseline (i.e., number of occurrences, NO). NO values were computed on two-second long windows. Six non-overlapped windows were selected, one just before and five just after the last unsuccessful shock. RESULTS: Immediately after the shock most of the patients exhibited an increase in the organization patterns. This increase was more evident in those patients with rather disorganized patterns and higher energy threshold. This effect fades within a few seconds after the shock delivery. CONCLUSIONS: Our data confirm the idea that the electrical shock causes a widespread extinction of electrical wavefronts, which regenerates after the shock. Since an increase of organization may lead to a reduction of energy threshold, a potential application of these findings might consist in the delivery of multiple subthreshold shocks instead of a single one.

Measure of synchronisation of right atrial depolarisation wavefronts during atrial fibrillation.

A new index of synchronisation (IS) between the electrical activity of pairs of close atrial sites during atrial fibrillation (AF) is introduced. The index assesses the probability of finding synchronous activations in intra-atrial bipolar electrograms and is based on the assumption that two activations closely spaced in time are likely to belong to the same depolarisation wavefront. A dedicated statistical treatment to test this hypothesis is also illustrated. Experimental data were obtained using a multipolar basket catheter in the right atrium in 20 patients during normal sinus rhythm (NSR), atrial flutter (AFL, one patient), high-frequency pacing (HFP, two patients) and chronic AF (17 patients), and 30 segments were obtained from each. From the 24 pairs of bipoles, a single averaged IS and its standard deviation were extracted. The IS was 1 in NSR and HFP and 0.95 +/- 0.02 during AFL. During AF, the IS provided a quantitative measure of the degree of coupling of various atrial sites. The IS varied significantly among the recording sites (range 0.38-0.96), showing a patient-dependent pattern, and decreased as the arrhythmia complexity increases. No temporal trends were observed for the IS values in any chronic AF patient. On average, in each site, the dispersion of the IS over time was lower than 32% of the mean, for all patients. Additional relevant features of the proposed index are its high temporal resolution (2s) and robustness to activation time estimation error, to missing or false detections and to the ever-changing pattern of propagation. The index of synchronisation is a descriptor of the electrophysiological properties of atrial tissues.

A novel heart/trunk simulator for the study of electromagnetic interference with active implantable devices.

This paper describes a portable heart simulator for the study of electromagnetic interference with active implantable devices. The simulator consists of plexiglas box divided into three chambers simulating the left atrium and the ventricles, plus a lateral compartment for the implantable device. The box is linked to a laptop computer by an analogue-to-digital convertor board, and the three chambers are monitored and driven by dedicated hardware and software interfaces. Synthetic endocardial atrial and ventricle signals for 13 cardiac rhythms are stored in the computer. They are applied to the cardiac chambers by AgCl plates. Sensing electrodes are in the form of AgCl needles inserted in saline. The simulator was able to demonstrate the behaviour of three pacemakers tested in the absence and presence of electromagnetic interference, generated by mobile phones (European GSM 900 and 1800 MHz) that emitted up to 2W (1 W at 1800 MHz). Pacemakers can be programmed with sensitivity from 0.1 mV to 5 mV, pulse width from 0.1 ms to 1.5 ms and pulse amplitude from 0.5 V to 5 V. The structural separation in three cardiac chambers (plus the one for the device) allowed a fast analysis procedure for dual- and tri-chamber implantable devices.

Transient phase locking patterns among respiration, heart rate and blood pressure during cardiorespiratory synchronisation in humans.

The interactions between respiration, heart rate and blood pressure variability (HRV, BPV), are considered to be of paramount importance for the study of the functional organisation of the autonomic nervous system (ANS). The aim of the reported study is to detect and classify the intermittent phase locking (PL) phenomena between respiration, HRV and BPV during cardiorespiratory synchronisation experiments, by using the following time-domain techniques: Poincaré maps, recurrence plots, time-space separation plots and frequency tracking locus. The experimental protocol consists of three stages, with normal subjects in paced breathing at 15, 12 and 8 breaths min-1. Transient phenomena of coordination between respiration and the major rhythms of HRV and BPV (low and high frequency, LF and HF) have been detected and classified: no interaction between LF and HF rhythms at 15 breaths min-1; short time intervals of stable 1:2 frequency and phase synchronisation during the 12 breaths min-1 stage; 1:1 PL during the 8 breaths min-1 stage. 1:1 and 1:2 PL phenomena occurred when the respiration frequency was quite close to the LF frequency or when it was about twice the LF frequency, respectively. The complex organisation of the ANS seems to provoke transient rather than permanent PL phenomena between the co-ordinating components of respiration and cardiovascular variability series.

Linear and non-linear analysis of atrial signals and local activation period series during atrial-fibrillation episodes.

Linear and non-linear indexes for the characterisation of the dynamics in atrial signals (AS) and local atrial period (LAP) series are assessed in different atrial fibrillation (AF) episodes as defined by Wells. Parameters include the linear index obtained from the cross-correlation function (CCF) between ASs and the non-linear synchronisation (S) index based on the mutual corrected conditional entropy (MCCE). Regularity (R) was computed on single-lead AS. In addition, the level of predictability (LP) and the regularity of LAP series were computed. It was found that the level of synchronisation between ASs decreased passing from type-I to type-II AF when using linear (CCF: 0.90 +/- 0.10 against 0.44 +/- 0.18; p<0.001) and non-linear (S: 0.22 +/- 0.10 against 0.05 +/- 0.03; p<0.001) indexes. The regularity index (in normal sinus rhythm (NSR): 0.30 +/- 0.08; in AF-I: 0.19 +/- 0.10; in AF-II: 0.09 +/- 0.02; NSR against AF-I p<0.001; AF-I against AF-II p<0.001) and level of predictability (in NSR: 65 +/- 18; in AF-I: 27 +/- 13; in AF-II 7 +/- 6; NSR against AF-I p<0.001; AF-I against AF-II p<0.001) significantly decreased in the LAP series passing from NSR to AF-II. The proposed parameters succeeded in discriminating the different dynamics which characterised AS and LAP series during different kinds of AF episodes.

Spontaneous and forced non-linear oscillations in heart period: role of the sino-atrial node.

The aim of this study is to investigate whether and to which extent the non-linearity of the sino-atrial node contributes to the complex interactions between autonomic control and heart period. A non-linear model of the autonomic control on the sino-atrial node has been analyzed under particular experimental conditions: the autonomic nervous system was forced to act at established frequencies, by a controlled breathing procedure and a non-invasive periodic modulation of carotid baroreceptors. We quantify the non-linear coupling between the stimuli and both the experimental and the simulated heart period fluctuations by using the recurrence plot quantification analysis. Our results show that the non-linear interaction between external stimuli and heart period fluctuations is due to a certain extent to the non-linear features of the sino-atrial node.

Coupling patterns between spontaneous rhythms and respiration in cardiovascular variability signals.

We performed a quantitative study of coupling patterns between respiration and spontaneous rhythms of heart rate and blood pressure variability signals by using the Recurrence Quantification Analysis (RQA). We applied RQA to both simulated and experimental data obtained in control breathing at three different frequencies (0.25, 0.20, and 0.13 Hz) from ten normal subjects. RQA succeeded in quantifying different degrees of non-linear coupling associated to several interference patterns. We found higher degrees of non-linear coupling when the respiratory frequency was close to the spontaneous Low Frequency (LF) rhythm (0.13 Hz), or almost twice the LF frequency (0.2 Hz), whereas weaker coupling was observed when the respiratory frequency was 0.25 Hz. Clinical applications of our approach should focus on new experimental protocols, featuring the stimulation of one of the two branches of the autonomic nervous system (ANS) or aimed at the analysis of pathologies linked to the ANS.

Extraction of physiological and clinical information from intra-atrial electrograms during atrial fibrillation: review of methods.

This paper presents a review of the evolution of methods and algorithms for the analysis of intra-atrial recordings, with special emphasis to the extraction of physiological and clinical information during atrial fibrillation. The principal time-domain and frequency-domain methods of electrogram analyses are described, and their physiological interpretation and clinical applications are discussed. In addition, the recent findings from complex system theory and chaos theory approaches are highlighted.