T-wave morphology analysis of competitive athletes.

BACKGROUND: T-wave morphology has been shown to be more sensitive than QT and QTc interval to describe repolarization abnormalities. The electrocardiogram (ECG) performed in athletes may manifest abnormalities, including repolarization alterations. The aim of this study was to investigate the characteristics of T-wave morphology features in athletes. METHODS: Eighty male elite athletes, consisting of 40 Tour de France cyclists (age 27±5years), 40 soccer players (age 26±6years) and 40 healthy men (age 27±5years) were included. RESULTS: Sinus bradycardia, left ventricular (LV) hypertrophy, incomplete right bundle branch block and early repolarization were documented in 25 %, 20%, 13% and 14% of athletes, respectively. ECG criteria for LV hypertrophy in 12-lead ECG were more common in cyclists (35%) than in soccer players (5%), P<0.0001. Cyclists and soccer players had significantly longer RR interval, and repolarization features than the control group. CONCLUSIONS: T-wave morphology of athletes is different from non-athletes, depending of the sport. Decreased potassium current in cardiomyocytes associated with LVH may contribute to these changes.

QT interval prolongation during spontaneous episodes of hypoglycaemia in type 1 diabetes: the impact of heart rate correction.

AIMS/HYPOTHESIS: Prolongation of the heart rate corrected QT interval (QTc) is seen during episodes of hypoglycaemia in type 1 diabetes. We studied the relationship between spontaneous hypoglycaemia and the QT interval and hypothesised that the choice of heart rate correction affects the observed change in QTc. METHODS: Twenty-one participants with type 1 diabetes (aged 58 +/- 10 years with duration of diabetes 34 +/- 12 years) had continuous glucose and ECG monitoring for 72 h. QT and RR intervals were measured during hypoglycaemia (blood glucose or continuous glucose measurements

The effect of sertindole on QTD and TPTE.

OBJECTIVE: Recent research suggests that other surrogate markers than QTc, including QTc dispersion and Tpeak-Tend, may better correlate with cardiac arrhythmia risk. While sertindole significantly prolongs the QTc interval, the effects on other markers of arrhythmia risk, such as QTc dispersion and Tpeak-Tend are unknown. METHOD: Digital 12-lead ECG was recorded at baseline and at steady-state in 37 patients switched to sertindole. ECG was analysed for Fridericia-corrected QT duration (QTcF), QT dispersion and Tpeak-Tend. RESULTS: From a baseline QTcF of 407 +/- 22 ms, mean QTcF prolongation during sertindole treatment was 20 +/- 23 ms, P < 0.01. No effect on QTc dispersion was found (-1 +/- 11 ms; P = 0.41). No increased duration of the Tpeak-Tend interval from baseline was found (+7 +/- 21 ms; P = 0.05). CONCLUSION: These findings might be related to the absence of confirmed Torsade de Pointes (TdP) cases related to sertindole exposure, despite sertindole's QTc prolonging effects.

Automated pre-ejection period variation indexed to tidal volume predicts fluid responsiveness after cardiac surgery.

BACKGROUND: Reliable continuous monitoring of fluid responsiveness is an unsolved issue in patients ventilated with low tidal volume. We hypothesised that variations in the pre-ejection period (PEP) defined as the time interval between electrocardiogram (ECG) R-wave and onset of systolic upstroke in arterial blood pressure could reliably predict fluid responsiveness in patients ventilated with moderately low tidal volume. Furthermore, we hypothesised that indexing dynamic parameters to tidal volume would improve their prediction. The aim was to refine and automate a previously suggested algorithm for PEP variation (DeltaPEP) and to test this new parameter indexed to tidal volume (PEPV), as a marker of fluid responsiveness along with central venous pressure (CVP), pulse pressure variation (PPV) and DeltaPEP. Additionally, the aim was to evaluate the concept of indexing dynamic parameters to tidal volume. METHODS: Arterial pressure, CVP, ECG and cardiac index (CI) were acquired from 23 mechanically ventilated post-cardiac surgery patients scheduled for volume expansion. PEPV, PPV and DeltaPEP were extracted. RESULTS: Using responder/non-responder classification (response=change in CI>+15%), sensitivity and specificity were 100% and 83%, respectively, for PEPV, 94% and 83% for DeltaPEP, and 94% and 83% for PPV. CVP offered no relevant information. Tidal volume indexing improved sensitivity for DeltaPEP to 100%. CONCLUSION: In this study in post-cardiac surgery patients, a refined parameter, PEPV, predicted fluid responsiveness better than PPV and DeltaPEP. Our results suggest that dynamic parameters using variations in PEP should be indexed to tidal volume.

Coronary artery disease risk reclassification by a new acoustic-based score.

To determine the potential of a non-invasive acoustic device (CADScor®System) to reclassify patients with intermediate pre-test probability (PTP) and clinically suspected stable coronary artery disease (CAD) into a low probability group thereby ruling out significant CAD. Audio recordings and clinical data from three studies were collected in a single database. In all studies, patients with a coronary CT angiography indicating CAD were referred to coronary angiography. Audio recordings of heart sounds were processed to construct a CAD-score. PTP was calculated using the updated Diamond-Forrester score and patients were classified according to the current ESC guidelines for stable CAD: low < 15%, intermediate 15-85% and high > 85% PTP. Intermediate PTP patients were re-classified to low probability if the CAD-score was ≤ 20. Of 2245 patients, 212 (9.4%) had significant CAD confirmed by coronary angiography ( ≥ 50% diameter stenosis). The average CAD-score was higher in patients with significant CAD (38.4 ± 13.9) compared to the remaining patients (25.1 ± 13.8; p < 0.001). The reclassification increased the proportion of low PTP patients from 13.6% to 41.8%, reducing the proportion of intermediate PTP patients from 83.4% to 55.2%. Before reclassification 7 (3.1%) low PTP patients had CAD, whereas post-reclassification this number increased to 28 (4.0%) (p = 0.52). The net reclassification index was 0.209. Utilization of a low-cost acoustic device in patients with intermediate PTP could potentially reduce the number of patients referred for further testing, without a significant increase in the false negative rate, and thus improve the cost-effectiveness for patients with suspected stable CAD.

Quasi-trapezoidal pulses to selectively block the activation of intrinsic laryngeal muscles during vagal nerve stimulation.

The stimulation of the vagus nerve has been used as an anti-epileptic treatment for over a decade, and its use for depression and chronic heart failure is currently under investigation. Co-activation of the intrinsic laryngeal muscles may limit the clinical use of vagal stimulation, especially in the case of prolonged activation. To prevent this, the use of a selective stimulation paradigm has been tested in seven acute pig experiments. Quasi-trapezoidal pulses successfully blocked the population of the largest and fastest vagal myelinated fibers being responsible for the co-activation. The first response in the vagus compound action potential was reduced by 75 +/- 22% (mean +/- SD) and the co-activated muscle action potential by 67 +/- 25%. The vagal bradycardic effects remained unchanged during the selective block, confirming the leading role of thin nerve fibers for the vagal control of the heart. Quasi-trapezoidal pulses may be an alternative to rectangular pulses in clinical vagal stimulation when the co-activation of laryngeal muscles must be avoided.

Classification of the long-QT syndrome based on discriminant analysis of T-wave morphology.

The long QT syndrome (LQTS) is a genetic disorder, typically characterized by a prolonged QT interval in the ECG due to abnormal cardiac repolarization. LQTS may lead to syncopal episodes and sudden cardiac death. Various parameters based on T-wave morphology, as well as the QT interval itself have been shown to be useful discriminators, but no single ECG parameter has been sufficient to solve the diagnostic problem. In this study we present a method for discrimination among persons with a normal genotype and those with mutations in the KCNQ1 (KvLQT1 or LQT1) and KCNH2 (HERG or LQT2) genes on the basis of parameters describing T-wave morphology in terms of duration, asymmetry, flatness and amplitude. Discriminant analyses based on 4 or 5 parameters both resulted in perfect discrimination in a learning set of 36 subjects. In both cases cross-validation of the resulting classifiers showed no misclassifications either.

Influence of variable nerve fibre geometry on the excitation and blocking threshold. A simulation study.

The aim of the study was to investigate how variable fibre geometry influences the excitation and blocking threshold of an undulating peripheral nerve fibre. The sensitivity of the excitation and blocking thresholds of the nerve fibres to various geometric and stimulation parameters was examined. The nerve fibres had a spiral shape (defined by the undulation wavelength, undulation amplitude and phase), and the internodal length varied. Diameter-selective stimulation of nerve fibres was obtained using anodal block. Simulation was performed using a two-part simulation model: a volume conductor model to calculate the electrical potential distribution inside a tripolar cuff electrode and a model of a peripheral undulating human nerve fibre to simulate the fibre response to stimulation. The excitation threshold of the undulating fibres was up to 100% higher than the excitation threshold of the straight fibres. When a nerve was stimulated with long pulses, which are typically applied for anodal block (> 400 micros), the blocking threshold of the undulating fibres was up to four times higher than the blocking threshold of the straight fibres. Dependencies of the excitation threshold on geometric and stimulation parameters were the same as for a straight fibre. Dependencies of the blocking threshold on geometric and stimulation parameters were different compared with a straight fibre. Owing to the fibre undulation and variable internodal length, the blocking threshold and the minimum pulse duration to obtain anodal block were generally different in the proximal and distal directions. Owing to variable fibre geometry, the excitation threshold varied by up to +/- 40% of the mean value, and the blocking threshold varied by up to +/- 60 % of the mean value. Owing to undulation, the blocking threshold of large fibres could be higher than the blocking threshold of small-diameter fibres, even if they had the same geometry. The results indicate that, during skeletal muscle stretching and contracting or during variation in joint angle, the excitation and blocking thresholds of the nerve fibres change owing to variations in fibre geometry. A straight fibre model could be too simple for modelling the response of peripheral nerve fibres to electrical stimulation.

MR assessment of the normal position of the spinal cord in the spinal canal.

PURPOSE: To investigate intradural geometry, which strongly influences the effects of epidural spinal cord stimulation. METHODS: Axial MR images with turbo spin-echo were made of 26 healthy subjects at C-4 through C-6, T-5 and T-6, and T-11 and T-12, at T-11 and T-12 both in the supine and the prone position. Measurements were made of the dorsomedial and the ventromedial cerebrospinal fluid layer and the anteroposterior and transverse sizes of both the spinal cord and the dural sac. The samples of all variables were analyzed statistically. The distance between spinal and vertebral midline was also determined. RESULTS: The dorsal cerebrospinal fluid layer was 1.5 to 4.0 mm at C-4 through C-6 and 4.0 to 8.5 mm at T-5 and T-6. At T-11 it was 2.0 to 6.0 mm in the supine position and was increased by approximately 2.2 mm in the prone position. At T-12 these values were 1.5 to 4.5 mm and approximately 3.4 mm, respectively. Differences between the spinal and vertebral midline up to 1.5 to 2.0 mm occurred in approximately 40% of the images. CONCLUSIONS: Because there are variations of the dorsal cerebrospinal fluid layer among subjects by more than a factor of 2, and significant variations of the mediolateral position of the spinal cord, information on these parameters in patients will be essential for the optimal application of epidural spinal cord stimulation.

Calculation of electric fields in a multiple cylindrical volume conductor induced by magnetic coils.

A method is presented for calculating the electric field, that is induced in a cylindrical volume conductor by an alternating electrical current through a magnetic coil of arbitrary shape and position. The volume conductor is modeled as a set of concentric, infinitely long, homogeneous cylinders embedded in an outer space that extends to infinity. An analytic expression of the primary electric field induced by the magnetic coil, assuming quasi-static conditions, is combined with the analytic solution of the induced electric scalar potential due to the inhomogeneities of the volume conductor at the cylindrical interfaces. The latter is obtained by the method of separation of variables based on expansion with modified Bessel functions. Numerical results are presented for the case of two cylinders representing a nerve bundle with perineurium. An active cable model of a myelinated nerve fiber is included, and the effect of the nerve fiber's undulation is shown.

Evaluation of the cable model for electrical stimulation of unmyelinated nerve fibers.

The cable model, used to calculate the membrane potential of an unmyelinated nerve fiber due to electrical stimulation, is reexamined under passive steady-state conditions. The validity of two of the assumptions of the cable model are evaluated, namely that the membrane potential be a function of the axial coordinate only and that the extracellular potential due to the presence of the nerve fiber be negligible. The membrane potential calculated from the passive steady-state cable model is compared with the membrane potential obtained from an analytical three-dimensional (3-D) volume conductor model of a nerve fiber. It is shown that for very small electrode-fiber distances (of only a few fiber radii), both assumptions are violated and the two models give quite different results. Over a wide range of the electrode-fiber distance (about 0.1 mm to 1 cm), both assumptions are fulfilled and the two models give approximately the same results. For very large distances (more than 10 cm, independent of fiber diameter) only the second assumption is satisfied, but a modification of the activating function of the cable model allows to calculate the membrane potential in agreement with the 3-D model.

Excitation of dorsal root fibers in spinal cord stimulation: a theoretical study.

In epidural spinal cord stimulation it is likely that not only dorsal column fibers are activated, but that dorsal root fibers will be involved as well. In this investigation a volume conductor model of the spinal cord was used and dorsal root fibers were modeled by an electrical network including fiber excitation. The effects of varying some geometrical fiber characteristics, as well as the influence of the dorsal cerebrospinal fluid layer and the electrode configuration on the threshold stimulus for their excitation, were assessed. The threshold values were compared with those of dorsal column fibers. The results of this modeling study predict that, besides the well known influence of fiber diameter, the curvature of the dorsal root fibers and the angle between these fibers and the spinal cord axis were of major influence on their threshold values. Because of these effects, threshold stimuli of dorsal root fibers were relatively low as compared to dorsal column fibers. Excitation of the dorsal root fibers occurred near the entry point of the fibers.

Epidural spinal cord stimulation: calculation of field potentials with special reference to dorsal column nerve fibers.

The effect of electrical stimulation with several electrode combinations on nerve fibers with different orientations in the spinal cord was investigated by computing the steady-state field potentials and activating functions. At first an infinite homogeneous model was used while secondly the spinal cord and its surrounding tissues were modeled as an inhomogeneous anisotropic volume conductor. The effect of mediodorsal epidural stimulation was calculated. It was concluded that with cathodal stimulation, mediodorsally in the epidural space, longitudinal fibers are depolarized, but dorsoventral ones are hyperpolarized. With anodal stimulation the opposite will occur. It was found that parameters substantially affecting the potential distribution in the dorsal columns are the conductivity of the white matter and the width and the conductivity of the csf layer.

Recruitment of dorsal column fibers in spinal cord stimulation: influence of collateral branching.

An electrical network model of myelinated dorsal column nerve fibers is presented. The effect of electrical stimulation was investigated using both a homogeneous volume conductor and a more realistic model of the spinal cord. An important feature of dorsal column nerve fibers is the presence of myelinated collaterals perpendicular to the rostro-caudal fibers. It was found that transmembrane potentials, due to external monopolar stimulation, at the node at which a collateral is attached, is significantly influenced by the presence of the collateral. It is concluded that both excitation threshold and blocking threshold of dorsal column fibers are decreased up to 50% compared to unbranched fibers.

A modeling study of nerve fascicle stimulation.

A nerve stimulation model has been developed, incorporating realistic cross-sectional nerve geometries and conductivities. The potential field in the volume conductor was calculated numerically using the variational method. Nerve fiber excitation was described by the model of McNeal. Cross-sectional geometries of small monofascicular rat common peroneal nerve and multifascicular human deep peroneal nerve were taken as sample geometries. Selective stimulation of a fascicle was theoretically analyzed for several electrode positions: outside the nerve, in the connective tissue of the nerve, and inside a fascicle. The model results predict that the use of intraneural or even intrafascicular electrodes is necessary for selective stimulation of fascicles not lying at the surface of the nerve. Model predictions corresponded with experimental results of Veltink et al. on intrafascicular and extraneural stimulation of rat common peroneal nerve and to results of McNeal and Bowman on muscle selective stimulation in multifascicular dog sciatic nerve using an extraneural multielectrode configuration.

Selective stimulation of sacral nerve roots for bladder control: a study by computer modeling.

The aim of this study was to investigate theoretically the conditions for the activation of the detrusor muscle without activation of the urethral sphincter and afferent fibers, when stimulating the related sacral roots. Therefore, the sensitivity of excitation and blocking thresholds of nerve fibers within a sacral root to geometric and electrical parameters in tripolar stimulation using a cuff electrode, have been stimulated by a computer model. A 3-D rotationally symmetrical model, representing the geometry and electrical conductivity of a nerve root surrounded by cerebrospinal fluid and a cuff was used, in combination with a model representing the electrical properties of a myelinated nerve fiber. The electric behavior of nerve fibers having different diameters and positions in a sacral root was analyzed and the optimal geometric and electrical parameters to be used for sacral root stimulation were determined. The model predicts that an asymmetrical tripolar cuff can generate unidirectional action potentials in small nerve fibers while blocking the large fibers bidirectionally. This result shows that selective activation of the detrusor may be possible without activation of the urethral sphincter and the afferent fibers.

Significance of the spinal cord position in spinal cord stimulation.

The effects of the antero-posterior and medio-lateral positions of the spinal cord in the dural sac on the perception threshold and paresthesia coverage in spinal cord stimulation were analyzed. The distributions of the dorsal cerebrospinal fluid (CSF) layer thickness, measured from transverse MR scans of normal subjects at various spinal levels, were used to calculate the distributions of threshold voltages for the stimulation of spinal nerve fibers by a computer model. These theoretical threshold distributions were shown to fit well to the corresponding distributions of perception threshold measured in patients. It is concluded that the thickness of the dorsal csf layer is the main factor determining the perception threshold and paresthesia coverage in spinal cord stimulation: an increasing thickness raises the threshold and reduces the coverage, and vice versa. The effects of an asymmetrical electrode position with respect to the spinal cord midline were also analyzed by computer modeling. It is concluded that a lateral asymmetry of less than 1 mm gives a significant reduction of perception threshold and may result in unilateral paresthesiae.

Transverse tripolar spinal cord stimulation: theoretical performance of a dual channel system.

A new approach to spinal cord stimulation is presented, by which several serious problems of conventional methods can be solved. A transverse tripolar electrode with a dual-channel voltage stimulator is evaluated theoretically by means of a volume conductor model, combined with nerve fibre models. The simulations predict that a high degree of freedom in the control of activation of dorsal spinal pathways may be obtained with the described system. This implies an easier control of paraesthesia coverage of skin areas and the possibility to correct undesired paraesthesia patterns, caused by lead migration, tissue growth, or anatomical asymmetries, for example, without surgical intervention. It will also be possible to preferentially activate either dorsal column or dorsal root fibres, which has some important clinical advantages. Compared to conventional stimulation systems, the new system has a relatively high current drain.

Magnetic and electrical stimulation of undulating nerve fibres: a simulation study.

Mathematical models of myelinated nerve fibres are highly stylized abstractions of real nerve fibres. For example, nerve fibres are usually assumed to be perfectly straight. Such idealizations can cause discrepancies between theoretical predictions and experimental results. One well-known discrepancy is that the currently used models predict (contradictory to experimental findings) that an activation of nerve fibres is not possible with a pure transverse electric field. This situation occurs when a magnetic coil is placed symmetrically above a straight nerve fibre for magnetic nerve stimulation, or when an anode and a cathode are placed equidistantly on a line perpendicular to the fibre in the case of electrical stimulation. It is shown that this discrepancy does not occur if the physiological undulation of peripheral nerve fibres is included in the models. Even for small undulation amplitudes (e.g. 0.02 mm), it is possible to activate the fibre in these positions. For physiological undulations, as found in the literature, and favourable (off-centre) positions, the typical reduction of the thresholds is in a range between one and five, compared with perfectly straight fibres.

Measurement of the performance of nerve cuff electrodes for recording.

New designs of cuff electrodes for the recording of signals from peripheral nerves are typically tested in acute animal experiments before long-term evaluation takes place. A reproducible, cost-effective and fast method is presented for evaluating cuff electrodes with respect to signal amplitude, noise rejection, and, in some cases, selectivity, as an alternative to acute in vivo experiments. Comparisons with a computer model and with signals obtained from rabbit tibial nerve give good agreement with the new method. It is shown that an imperfect closure of the cuff around the nerve can easily lead to more than 50% loss of the signal amplitude. Noise from sources external to the cuff is not significantly affected by the closing mechanism, but is strongly reduced by a tripolar cuff configuration as compared with a monopolar one (reduction factor 2.8 to 58, mean = 6.5, n = 6). In dual-channel cuffs, cross-talk is below 1.2% indicating a very high selectivity.