Wearable sensor systems: the challenges.

Given the soaring costs associated with the treatment of ever more prevalent chronic disease, it is widely agreed that a revolution is required in health care provision. It is often thought that the necessary technology already exists for the home-based monitoring of such patients and that it is other factors which are holding back the more widespread clinical uptake of these new tools. The authors suggest that the necessary sensor-related technologies are often not as advanced as may first appear; certainly they are generally not adequate for the robust, long-term monitoring of patients under real-life conditions. An additional problem is the evident efforts to apply a given sensor and related technology platform to any and all monitoring scenarios without sufficient consideration of patient needs and the clinical requirements. The authors review the key sensing platforms and suggest the applications for which they are best suited.

Capitalizing on knowledge for an adaptive user interface.

Hypermedia data browsing is a mean for improving information access. However, the overload and the heterogeneity of medical information, as well as the multitude of possible navigational paths, turn the consultation of data into a difficult task. We present in this paper a solution for the development of adaptive user interfaces in a hypermedia data browsing environment. It is based on the capitalization of the users knowledge in the decision-making process, expressed in terms of navigational paths and of data presentation modes that are customized to the user's preferences. This capitalization offers the user a way to reuse the cumulative experiences in browsing through patient records. We illustrate our approach with the implementation of HEMA, a clinical workstation prototype.

A neural network approach for predicting and modelling the dynamical behaviour of cardiac ventricular repolarisation.

Physiological signals are usually patient specific, and they are difficult to predict, especially for the cardiovascular system. New methods capable to be adapted to each case and to learn the singular behavior of heart functions should be developed to support physicians in their decision-making. One of the most widely studied relations is the QT-RR one, between the total duration of the ventricle activation and inactivation, and the heart rate. In the past, different studies were made to approach this relation in the steady state. In this paper, a new method for modeling and predicting the transient dynamic behaviour of QT interval in relation to changing RR intervals is presented using artificial neural networks.

Identification of post-myocardial infarction patients prone to ventricular tachycardia using time-frequency analysis of QRS and ST segments.

BACKGROUND: Late potentials (LPs) in the terminal portion of the QRS complex are commonly sought to identify post-myocardial infarction patients prone to ventricular tachyarrthythmias (VT) or sudden death. More recent time frequency signal processing tools have been shown to provide new parameters for the quantification of LPs and abnormal activities buried within the QRS complex. METHODS AND RESULTS: The study population comprised 23 myocardial infarction patients with documented sustained VT (MI+VT), 40 myocardial infarction patients without VT (MI - VT) and 31 normal subjects. The reproducibility of the method was tested in an additional set of 66 patients. The signal-averaged high-resolution electrocardiograms (HRECGs) were quantified by deconstructing the unfiltered X, Y and Z leads using a 511-orthogonal wavelet network. Using receiver operating characteristics (ROC) curves and discriminant analysis applied to the wavelet coefficients, we extracted the most significant wavelets to classify the post MI patients. These wavelets detected time-frequency alterations both in the ST segment and within the QRS complex, characterizing patients prone to VTs. The same statistical methods were applied to the conventional time-domain measurements. The combined application in our population of the orthogonal wavelet deconstruction method and discriminant analysis had 91% sensitivity and 95% specificity, an improvement of 22% and 25%, respectively, compared with the conventional time domain method. Reproducibility was 82%. CONCLUSIONS: In post-myocardial infarction patients, orthogonal wavelet transforms can detect alterations in high-frequency components within the QRS and ST segment. Our findings support the view that wavelet-related parameters are more relevant than those of the time domain method in predicting subsequent malignant tachyarrhythmias.

Dynamic analysis of dofetilide-induced changes in ventricular repolarization.

OBJECTIVE: To use dynamic electrocardiographic (ECG) techniques to study the influence of heart rate on dofetilide-induced QT prolongation among healthy volunteers. BACKGROUND: The extent to which heart rate modulates QT prolongation induced by the new class III antiarrhythmic drug dofetilide is a matter of debate. METHODS: Ten healthy volunteers underwent two 24-hour ECG recordings, one in the absence of dofetilide and the other after a single oral dose of 0.5 mg dofetilide. Two 4-hour periods were defined during the second recording: Dh, which corresponded to stable high concentration of the drug, and D1, which corresponded to low concentration of the drug. Corresponding baseline recording periods, Ch and C1, matched by time with Dh and D1 were selected from the control ECG recording in the absence of dofetilide. QT versus R-R relations were compared in the presence and absence of dofetilide. The QT versus R-R relation slope was used as an index of the rate dependence QT prolongation. Rate-independent changes in QT duration were also analyzed. RESULTS: During Dh, dofetilide induced a mean 12% lengthening of ventricular repolarization. Dynamic ECG analysis showed that this prolongation increased as R-R cycles became longer, a phenomenon known as reverse rate dependence. However, QT prolongation persisted at the shortest (600 ms) R-R cycle length that could be analyzed. During D1, dynamic ECG analysis showed a persistent, although small, effect of dofetilide on both QT prolongation (3%) and reverse rate dependence of this effect. CONCLUSIONS: Dofetilide prolongs QT duration, and this class III effect is influenced by heart rate. Although dofetilide-induced QT prolongation decreases when the R-R cycle shortens, this reverse rate dependence is only partial because marked QT prolongation persists at an R-R cycle of 600 ms. The results of our study indicated that dynamic ECG techniques can be useful in detection of subtle, drug-induced changes in the duration of ventricular repolarization.

Diagnostic performance of QT interval variables from 24-h electrocardiography in the long QT syndrome.

AIMS: The long QT syndrome is mainly defined by QT interval prolongation (QTc > 0.44s). However, data obtained in genotyped patients showed that resting QTc measurement alone may be inaccurate for ascertaining the phenotype. The aim of this study was to evaluate the diagnostic performance of QT interval rate-dependence in untreated chromosome 11-linked patients. METHODS: The study population consisted of 25 untreated long QT patients linked to chromosome 11 and 25 age- and gender-matched controls. QTc intervals were measured on 12-lead resting ECG recordings. From 24-h Holter recordings, the slope of the relationship between ventricular repolarization and heart rate was studied separately day and night to assess neural modulation. Mean heart rates and rate-dependences of QT and Q-maximum of T (QTm) intervals were compared between long QT patients and controls for both time periods. RESULTS: In both groups, the rate-dependences were modulated by day-night influences. When compared to controls, long QT patients showed a significant increase at night in QT/RR slopes (0.158 +/- 0.05 vs 0.117 +/- 0.03, P = 0.002) and QTm/RR slopes (0.163 +/- 0.05 vs 0.116 +/- 0.04, P = 0.0006). Multivariate analysis, adjusting QTc interval on age and gender, discriminated between long QT patients and controls with a 76% sensitivity and a 84% specificity. A 96% sensitivity and a 96% specificity were reached by taking into account the QTm/RR slope at night, the QTc interval and the mean heart rate during the day. CONCLUSION: QT interval variables obtained from 24-h ECG recordings improve long QT syndrome diagnosis by showing an increased nocturnal ventricular repolarization rate-dependence in genotyped chromosome 11-linked patients.

[Analysis of frequency-dependence of ventricular repolarisation by the Holter method in young adults. Influence of the autonomic nervous system on the rate-dependence of QT]. / Analyse de la fréquence-dépendance de la repolarisation ventriculaire par méthode Holter chez l'adulte jeune. Influence du système nerveux autonome sur la fréquence-dépendance de QT.

UNLABELLED: Adaptation of ventricular repolarization duration to heart rate provides additional information to the static duration of QT interval. METHODS: QT/RR relation and his slope were determined using 24-hour ECG recordings from 17 young male normal volunteers (mean age: 22 +/- 3 years). In order to determine the influence of the autonomic nervous system on the rate-dependence of QT, the authors compared the slopes obtained from recordings during the day and the night. Then, the respective rate-dependences of the entire QT interval (QTe) and its initial subdivision (QTa) and their correlations with parameters of heart rate variability were studied. RESULTS: the QTa/RR and QTe/RR relations were constantly linear, with very significant regression coefficients. The daytime QTa/RR and QTe/RR slopes were significantly steeper than the nighttime ones (0.138 +/- 0.035 vs 0.108 +/- 0.040, p < 0.05 for QTe/RR, 0.160 +/- 0.069 vs 0. 108 +/- 0.055, p < 0.01 for QTa/RR). The early part of QT showed a stronger rate-dependence than the global QT, but only at daytime (0.160 +/- 0.069 vs 0.138 +/- 0.035, p < 0.05). No correlation was found between rate dependences and heart rate variability parameters. CONCLUSION: the authors demonstrate, from ambulatory ECG recordings, the influence of the autonomic nervous system on the rate-dependence of ventricular repolarization in normal young adults, and a difference in rate-dependence between the entire QT interval and its initial part QTa, due to differences in autonomic nervous system tone. This heterogeneity should be taken to account in the study of pathological changes or drugs effects on ventricular repolarization.

Heterogeneous effect of quinidine on the ventricular depolarization process assessed by the spatial velocity electrocardiogram of the QRS complex. Preliminary report of a new investigative method.

The negative conduction effect of quinidine on each of the successive phases of the ventricular depolarization was investigated using an original noninvasive method: the spatial velocity electrocardiogram of the QRS complex (SVECG-QRS). We performed a randomized placebo-controlled trial in 10 healthy subjects with a single oral dose of quinidine (330 mg) or placebo. Electrocardiographic acquisition and processing (220 recordings for the complete trial) were performed using the Lyon vectorcardiographic program. For each SVECG-QRS curve, the position of seven specific points from A (onset of QRS) to G (end of QRS) were determined precisely. The six successive time intervals between these points (AB-FG) and five velocity values (B-F) were then calculated. The QRS complex was longer under quinidine than placebo (102.4 +/- 1.6 vs. 100.3 +/- 1.5 ms). The difference was at the periphery of statistical significance (p = 0.05), and this lack of statistical difference may be mainly due to the low serum levels of quinidine obtained at the peak of the concentration (1.46 +/- 0.4 mg/1). All six QRS time intervals were longer under quinidine, but only the BC interval was significantly different (9.3 +/- 1.1 vs. 18.8 +/- 1.1 ms; p < 0.05) suggesting a more pronounced negative conduction effect at the onset of ventricular depolarization. No significant modifications were observed for the velocity values. We conclude that (1) the negative conduction effect of quinidine is heterogeneous, but a further study with a higher dose of quinidine (concentration-dependent effect) is required to confirm this hypothesis and (2) the spatial velocity electrocardiogram of the QRS complex allows a detailed analysis of the ventricular conduction phases. The results of the measurement were found to be reproducible. This noninvasive tool could be used in clinical practice to assess effects of antiarrhythmic drugs on successive ventricular depolarization phases.

Interactive and dynamic ECG analysis. Is it just an IDEA or a clinically relevant approach?

The idea that it is possible to increase the overall electrocardiographic (ECG) diagnostic performance is developed in this paper, provided that different programs or methods and various data sources are combined and that the dynamicity of the patients' record is considered. This dynamicity consists of the following three dimensions: beat-to-beat changes within continuous recordings, changes between serial records, and clinical events. Data integration should be time- or event-related, and multisources data should interact. Interactive and dynamic ECG analysis (IDEA), however, can only be achieved if powerful clinical workstations are developed that access the right information, when and where needed, a challenge that the IDEA workstation intends to accomplish.

Are serial Holter QT, late potential, and wavelet measurement clinically useful?

Clinical centers are increasingly using new techniques such as Holter QT, late potential, and wavelet measurements. However, we lack validated databases for the assessment of the performance of the signal-processing methods and their reproducibility. Failure of the QT interval to adapt to changes in the heart rate is considered to be a more meaningful parameter than QT prolongation itself. In this study, different factors that may affect the reproducibility of QT and QTm (onset of the QRS to the maximum of T) measurement are analyzed: the incidence of sympathetic tone and parasympathetic activity on low- and high-frequency QT variability, the very low frequency dependency of the QT interval to changes in the R-R interval, changes in the heart's position, and measurement errors. Typical root-mean-square values of the beat-to-beat measurement errors in upright-position Holter recordings are only 1.5 ms for QT versus 3.4 ms for QTm. Although the dependence of the QT interval on the heart rate is well established, the method for rate correction of the QT interval remains controversial. None of the formulas for heart rate adjustment of the QT previously proposed provide complete correction for all of the rate influences involved due to "memory phenomenon"; that is, there is a time delay, ranging up to 3-4 minutes, between a change in heart rate and the subsequent change in the QT interval. This problem has been solved by developing patient-specific neural networks that are trained to "identify" the dynamic behavior of the QT interval (or QTm) as a function of the R-R interval in order to predict the beat-to-beat changes of the QT interval as a function of the measured beat-to-beat changes of the R-R interval. Computing the differences between the predicted and the measured QT interval will allow for the detection of any significant deviations, both in the steady-state and transient conditions. Recent developments in the analysis of the high-resolution electrocardiogram (HRECG) in the time domain and frequency domain, with emphasis on the assessment of the reproducibility of late potential and wavelet measurements, are also reported in this study. The two main causes of variability in HRECG analysis are physiology and, for time-domain analysis, intermanufacturer variability. Physiologic changes can be overcome by standardizing the clinical protocols and repeating the recordings. The most important technical requirement for the proper use of late potentials is to standardize the algorithm for the detection of QRS offset among different late potential analyzing machines so that clinical data can be exchanged. The recently introduced wavelet transform provides a fruitful alternative to the more classical time-domain methods. Preliminary results show an 8 to 15% performance improvement over conventional time-domain analysis for the stratification of the HRECG after myocardial infarction. Reproducibility is excellent, up to 100%, but needs to be assessed on larger populations matched for age, sex, and pathology.

Stratification of time-frequency abnormalities in the signal-averaged high-resolution ECG in postinfarction patients with and without ventricular tachycardia and congenital long QT syndrome.

Having developed sound mathematical techniques that allow precise mapping of cardiac signals in the time-frequency (TF) and time-scale planes, the next important issue is to extract from these representations information that best reflects the electrophysiologic and anatomic derangement unique to patients at risk of arrhythmias and other cardiac diseases. In this study, the authors present a new method that stratifies the magnitude of the TF transforms of abnormal cardiac signals into distinguishing features by comparing the means of the coefficients of the TF transforms of any study population to the corresponding means of a control population using a standard ANOVA technique. This results in a three-dimensional mapping of the high-resolution ECG into time, frequency, and P value components. Significant energy increases are given positive P values and depressed energies are given negative P values: these are ranked according to a color scale. The method was tested on two study populations: postmyocardial infarction patients with documented ventricular tachycardia (MI+VT, n = 23) and without (MI-VT, n = 40) and patients with congenital long QT syndrome (LQTS, n = 19). Two groups of healthy control subjects (n = 31 and n = 40) were used as a reference group matched for sex. The study results were based on the Morlet analyzing wavelets, with frequencies ranging from 40 to 250 Hz in 10 logarithmically progressing scales, and computed millisecond per millisecond over a 350-ms analyzing time window, starting from 100 ms before the onset of the QRS. The patients with MI+VT displayed significantly increased high-frequency components in the 40-250-Hz frequency range, corresponding to prolonged QRS duration and late potentials in the area from 80 to 150 ms after QRS onset. Significantly depressed energy (P < 10(-4)) was also observed for the 40-106-Hz frequency range in the first 50 ms of the QRS complex, mainly in lead Y and in the magnitude vector. In patients with LQTS, significant modifications (P < 10(-2)) were observed in the first half of the QRS and in the ST-segment, in all leads, revealing anomalies in the genesis of the ventricular depolarization and repolarization processes. In conclusion, the authors propose a new method for the stratification of abnormal TF components occurring in the signal-averaged high-resolution electrocardiogram of patients at risk of VT and fibrillation under different pathologic conditions.

CAVIAR: a tool to improve serial analysis of the 12-lead electrocardiogram.

An important part of an electrocardiogram (ECG) interpretation is the comparison between the present ECG and earlier recordings. The purpose of the present study was to evaluate a combination of two computer-based methods, synthesized vectorcardiogram (VCG) and CAVIAR, in this comparison. The methods were applied to a group of 38 normal subjects and to a group of 36 patients treated with anthracyclines. A fraction of these patients are likely to develop cardiac injury during or after the treatment, since anthracyclines are known to cause heart failure and cardiomyopathy. Two ECGs were recorded on each patient, one before and one after the treatment. On each normal subject, two ECGs were recorded with an interval of 8-9 years. A synthesized VCG was calculated from each ECG and the two synthesized VCGs from each subject were analysed with the CAVIAR method. The CAVIAR analysis is a quantitative method and normal limits for four measurements were established using the normal group. Values above these limits were more frequent in the patient group than in the normal group. The conventional ECGs were also analysed visually by an experience ECG interpreter without knowledge of the result of the CAVIAR analysis. No significant serial changes were found in 10 of the patients with high CAVIAR values. Changes in the ECGs were found in two patients with normal CAVIAR values. In summary, synthesized VCG and CAVIAR could be used to highlight small serial changes that are difficult to find in a visual analysis of ECGs.

Management of serial ECGs and control strategies for the comparison process.

Serial ECG management and control of the comparison process should be dynamically driven by patient data. The functional architecture requirements are specified for a computerized ECG processing system integrating serial analysis. The concepts of reference investigations and temporal events are first explained. A conceptual reference model is proposed which stratifies the serial analysis process into a few generic strategies which will be instantiated into several types of serial comparison processing tasks as a function of the clinical evolution of the patient. This model is an extension of the OEDIPE core data model developed and implemented during the AIM #2026 project.

Clinical relevance of assessing QT dynamicity in Holter recordings.

Ventricular repolarization (VR) duration is an electrophysiologic parameter that is poorly explored in the conventional electrocardiogram. The heart rate (HR) and the autonomic nervous system (ANS) condition its variations. The static QT measurement in the surface electrocardiogram and its correction using the Bazett formula constitute inadequate tools. The three-dimensional Holter recordings and their computerized analysis are better adapted to assess the dynamicity of VR, a relevant image of the myocardial state. QT and RR values are linearly correlated over 24 hours, but this does not allow one to study specifically the respective roles of HR and ANS on repolarization changes. To do so, it is necessary to select appropriately the QRST complexes according to their environment: not only the last RR cycle but the mean HR over the preceding minutes, and the circadian influences must be controlled to differentiate the role of the short- and long-term influences. Combining the ATREC and the CAVIAR softwares now permits control of both time and space dimensions and to measurement of the QT variations with a precision of the order of 1 ms, a performance necessary to assess tiny but meaningful changes. The QT interval is shorter, and the slope of the QT/RR regression line is steeper at daytime compared with night, and many situations modify this normal behavior. Aging lengthens the QT interval and reduces the day-to-night differences of QT duration and dynamicity. In contrast with duration, dynamicity does not depend on gender. Any heart disease, left ventricular hypertrophy, or heart failure alter QT dynamicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiologic effects of a potassium channel activator (pinacidil) on repolarization parameters in healthy volunteers: a surface ECG study.

About a quarter to a third of patients receiving pinacidil, a new cyanoguanidine vasodilator, show ECG changes, in particular T-wave modifications that sometimes mimic myocardial ischemia. To investigate these changes, we performed a randomized placebo-controlled trial in 10 carefully selected, healthy subjects who received single oral doses of either pinacidil (25 mg), quinidine (330 mg), and placebo. Quinidine, which induces specific modifications to the surface ECG signal, was used as an internal control. The complete experimental design involved five consecutive administrations of the drugs in random order: pinacidil (twice), quinidine (twice), and placebo (once), separated by a week-long washout period. Electrophysiologic data acquisition and signal analysis were performed with the Lyon vectocardiographic processing system. Pinacidil decreased T-wave amplitude (-0.26 +/- 0.1 mV) significantly as compared with placebo (-0.14 +/- 0.06 mV), but did not change the duration of the T-wave. Although the cardiac rate increased with pinacidil, the QTc interval remained constant. Conversely, quinidine did not modify the RR interval but significantly increased duration of the T-wave (+67 +/- 20 ms) and QTc interval (+53 +/- 13 ms) as compared with placebo (+17 +/- 13 and +18 +/- 11 ms). In addition, no specific ischemic changes to the T-loop were observed with pinacidil. The modifications to the surface ECG signal caused by pinacidil appear to be drug-specific and related to its electrophysiologic properties rather than involving any ischemic mechanism. Such an approach may be useful for describing morphologic ECG changes caused by new drugs and identifying possible underlying electrophysiologic mechanism(s), which should then be confirmed in further studies.

New trends in serial ECG analysis.

The prerequisite for future development and assessment of serial electrocardiographic analysis programs is the availability of easy to use database management systems for storage and retrieval of electrocardiographic data and results and efficient means for electronic interchange of digital electrocardiographic data. The basic aim of project 2026 of the European program for advanced informatics in medicine is to encourage "open European data interchange and processing for electrocardiography" (OEDIPE) and to provide objective decision support techniques in the field of quantitative electrocardiology. The final objective is to develop demonstration systems for the follow-up evaluation of (1) selected populations with heart disease, (2) integrating serial analysis, (3) decision support, (4) open databases, and (5) communication protocols, which will foreshadow large-scale monitoring of ambulatory or critically ill patients at home, during their transportation in an emergency vehicle, or during their stay in a hospital. The first-year objectives and achievements of the OEDIPE project are briefly described. Emphasis is put on the management of serial electrocardiographic records and data and on the control strategies for the management of the serial analysis process.

Quantitative assessment of 12-lead ECG synthesis using CAVIAR.

The objective of this study is to assess the performance of patient-specific segment-specific (PSSS) synthesis in QRST complexes using CAVIAR, a new method of the serial comparison for electrocardiograms and vectorcardiograms. A collection of 250 multi-lead recordings from the Common Standards for Quantitative Electrocardiography (CSE) diagnostic pilot study is employed. QRS and ST-T segments are independently synthesized using the PSSS algorithm so that the mean-squared error between the original and estimated waveforms is minimized. CAVIAR compares the recorded and synthesized QRS and ST-T segments and calculates the mean-quadratic deviation as a measure of error. The results of this study indicate that estimated QRS complexes are good representatives of their recorded counterparts, and the integrity of the spatial information is maintained by the PSSS synthesis process. Analysis of the ST-T segments suggests that the deviations between recorded and synthesized waveforms are considerably greater than those associated with the QRS complexes. The poorer performance of the ST-T segments is attributed to magnitude normalization of the spatial loops, low-voltage passages, and noise interference. Using the mean-quadratic deviation and CAVIAR as methods of performance assessment, this study indicates that the PSSS-synthesis algorithm accurately maintains the signal information within the 12-lead electrocardiogram.