Roberto Burattini

Adaptive Match Filter Based Method for Time vs. Amplitude Characterization of Microvolt ECG T-Wave Alternans

To develop a new method for non-invasive identification of patients prone to ventricular tachyarrhythmia and sudden cardiac death, an adaptive match-filter (AMF) was applied to detect and characterize T-wave alternans (TWA) in 200 coronary artery diseased (CAD) patients compared with 176 healthy (H) subjects. TWA was characterized in terms of duration (TWAD), amplitude (TWAA), and magnitude (TWAM, defined as the product of TWAD times TWAA). A criterion derived from these parameters, estimated over the H-population, allowed discrimination between a risk (TWA+) and a normality (NO TWA) zone in the TWAD-TWAA plane. To gain further ability to discriminate among different risk levels, the TWA+ zone was divided into four sub-zones respectively characterized by low duration and low amplitude (LDLA), low duration and high amplitude (LDHA), high duration and low amplitude (HDLA), and high duration and high amplitude (HDHA). With our methodology, 21 CAD-patients (10.5%) were identified as TWA+, 9 falling in the LDLA zone, 4 in the HDLA, 7 in the LDHA, and 1 in the HDHA. These results are in agreement with clinical expectations and pave the way to further clinical follow-up studies finalized to analyze pathophysiological implications and risk factors associated to each TWA+ zone.

Comparative analysis of methods for automatic detection and quantification of microvolt T-wave alternans

Microvolt T-wave alternans (TWA), consisting of every-other-beat changes in ECG T-wave morphology, is an index of susceptibility to malignant ventricular arrhythmias, requiring automatic techniques to be identified. Five of these, namely, fast-Fourier-transform spectral method (FFTSM), complex-demodulation method (CDM), modified-moving-average method (MMAM), Laplacian-likelihood-ratio method (LLRM) and adaptive-match-filter method (AMFM), were applied here to simulated and sample clinical data. The aim was to compare individual methods ability to properly identify stationary and time-varying TWA, avoiding false-positive detections. The MMAM provided false-positive TWA when applied to simulated ECGs affected by amplitude variability, but TWA. Stationary TWA was properly quantified by the MMAM and, occasionally, underestimated by all other methods. The AMFM properly identified time-varying TWA. By contrast, the FFTSM detected not-stationary TWA as stationary, the MMAM introduced a time-delay in the estimated TWA-amplitude signal, while the CDM and LLRM were reliable only in the presence of slow-varying TWA. Altogether, the AMFM accomplished the best compromise between the needs to avoid false-positive TWA and to detect and characterize true-positive TWA. Results of our simulation approach were useful to explain different TWA levels measured by each competing methods applied to sample Holter ECGs from healthy subjects and coronary artery disease patients.

Identification of canine coronary resistance and intramyocardial compliance on the basis of the waterfall model

This study was performed to elucidate the effects of cardiac contraction on coronary pressure-flow relations. On the basis of the waterfall mechanism, a lumped model of the coronary arterial system is presented consisting of a proximal (epicardial) compliance, a coronary resistance, and an intramyocardial compliance. A “back”-pressure, assumed to be proportional (constant k) to left ventricular pressure, impedes flow. From steady-state measurements of circumflex coronary artery flow and inflow pressure, together with left ventricular pressure, the values of the three model parameters and the constant k have been estimated. In the control condition proximal compliance is found to be 1.7×10−12 m4s2kg−1, intramyocardial compliance 110×10−12m4s2kg−1, and resistance 7.5×109kgm−4s−1. The proportionality constant k is close to unity. Effects of changes in left ventricular pressure and inflow pressure and the effect of vasoactive drugs on the parameters are also investigated. Changes in coronary resistance are always opposite to changes in intramyocardial compliance. Sensitivity analysis showed that epicardial compliance plays its major role during isovolumic contraction and relaxation; resistance plays a role throughout the cardiac cycle but is more important in diastole than in systole, whereas intramyocardial compliance plays a role in systole and in early diastole.

Insulin Sensitivity and Glucose Effectiveness Estimated by the Minimal Model Technique in Spontaneously Hypertensive and Normal Rats

This study was performed to compare glucose metabolism in anaesthetised spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) in an attempt to clarify whether this animal model of hypertension approximates the insulin‐resistant state seen in human hypertension. With this aim the minimal model of glucose kinetics was applied to glucose and insulin data derived from a 12‐sample, 120 min intravenous glucose tolerance test (IVGTT) performed in ten SHR and nine WKY rats under pentobarbital anaesthesia. This method provided two metabolic indices: the glucose effectiveness, SG, which quantifies the ability of glucose per se to enhance its rate of disappearance and to inhibit hepatic glucose production, and the insulin sensitivity, SI, which measures the ability of insulin to enhance plasma glucose disappearance and to inhibit hepatic glucose production. Systolic and diastolic arterial pressures in the SHR group were significantly higher (P < 0.0005) than in the WKY group. Mean SG and SI estimates from the SHR group (SG = 16.2 (± 2.0) × 10‐2 dl min‐1 kg‐1 and SI = 12.5 (± 1.9) × 10‐4 dl min‐1 kg‐1 (μU ml‐1)‐1) were not significantly different (P > 0.05) from mean estimates that characterised the WKY group (SG = 13.1 (± 1.5) × 10‐2 dl min‐1 kg‐1 and SI = 15.8 (± 4.3) × 10‐4 dl min‐1 kg‐1 (μU ml‐1)‐1). This result is in contrast with reported findings from humans in which insulin sensitivity is significantly reduced in the presence of hypertension.

Assessment of Physiological Amplitude, Duration, and Magnitude of ECG T-Wave Alternans

Background: An association between T‐wave alternans (TWA) and malignant ventricular arrhythmias is generally recognized. Because relatively low levels of TWA have also been observed in healthy (H) subjects, the question arises as to whether these are ascribable to noise and artifacts, or can be given the relevance of a physiological phenomenon characterizing a preclinical condition.

Automatic microvolt T-wave alternans identification in relation to ECG interferences surviving preprocessing

The aim was to investigate the effect of interferences surviving preprocessing (residual noise, baseline wanderings, respiration modulation, replaced beats, missed beats and T-waves misalignment) on automatic identification of T-wave alternans (TWA), an ECG index of risk for sudden cardiac death. The procedures denominated fast-Fourier-transform spectral method (FFTSM), complex-demodulation method (CDM), modified-moving-average method (MMAM), Laplacian-likelihood-ratio method (LLRM), and adaptive-match-filter method (AMFM) were applied to interferences-corrupted synthetic ECG tracings and Holter ECG recordings from control-healthy subjects (CH-group; n=25) and acute-myocardial-infarction patients (AMI group; n=25). The presence of interferences in simulated data caused detection of false-positive TWA by all techniques but the FFTSM and AMFM. Clinical applications evidenced a discrepancy in that the FFTSM and LLRM detected no more than one TWA case in each population, whereas the CDM, MMAM, and AMFM detected TWA in all CH-subjects and AMI-patients, with significantly lower TWA amplitude in the former group. Because the AMFM is not prone to false-positive TWA detections, the latter finding suggests TWA as a phenomenon having continuously changing amplitude from physiological to pathological conditions. Only occasional detection of TWA by the FFTSM and LLRM in clinics can be ascribed to their limited ability in identifying TWA in the presence of interferences surviving preprocessing.

Age-related analysis of glucose metabolism in spontaneously hypertensive and normotensive rats

This study was designed to investigate the effect of both hypertension and ageing on the efficiency of glucose metabolism. A 12‐sample, 120 min intravenous glucose tolerance test (IVGTT) was applied to 36 rats: two groups of nine young (12 weeks) spontaneously hypertensive and Wistar Kyoto rats (Y‐SHR and Y‐WKY group, respectively) and two groups of nine old (40 weeks) SHR and WKY rats (O‐SHR and O‐WKY group, respectively). Insulinaemia and glycaemia data were interpreted in terms of estimates of glucose effectiveness, SG, and insulin sensitivity, SI, provided by the minimal model of glucose kinetics. The possible link between insulin resistance and hypertension was investigated by comparing Y‐SHR vs. Y‐WKY and O‐SHR vs. O‐WKY groups. Comparison of O‐SHR vs. Y‐SHR and O‐WKY vs. Y‐WKY groups enabled us to investigate the role of age in the development of abnormalities in glucose metabolism. No significant differences (P > 0.05) were observed in the mean SG and SI estimates between SHR and age‐matched WKY groups. This finding indicates that exposure of SHR to high blood pressure levels does not necessarily lead to the development of insulin resistance and impaired glucose effectiveness. Similarly, no significant differences (P > 0.05) were observed in SG and SI estimates between old and young SHR and WKY groups. This finding indicates that, in this animal model of hypertension, insulin sensitivity and glucose effectiveness do not even deteriorate with ageing.

Lumped model of terminal aortic impedance in the dog

The aim of this study was the formulation of a minimal lumped model of the aortic impedance as seen in the abdominal aorta just downstream of the origin of renal arteries. At this location simultaneous measurements of pressure and flow were taken in four anesthetized and open-chest dogs (weight, 30.9±5.8 kg) under basal, vasodilated (sodium nitroprusside) and vasoconstricted (methoxamine) conditions. Using these measurements we identified and compared three lumped models, A, B, and C, with decreasing complexity from A to C. The frequency response of these models was given the general form of peripheral resistance,RP, multiplied by the ratio between (a) two zeros and two poles (model A); (b) two zeros and one pole (model B); and (c) one zero and one pole (model C).RP was calculated as the ratio of mean pressure to mean flow. The other model parameters (time constants, damping factors, and natural frequencies) were estimated by minimizing the sum of squared differences between experimental and model generated pulsatile flows. After parameter estimation, the F-test was applied to compare the goodness of data fit obtained from the three models. Results of this test and the analysis of parameter estimation errors indicated that model B was preferable with respect to models A and C. The analysis of general model performance was followed by a consideration of alternative specific model structures that are physically realizable. With the aid of a determined model structure we evaluated the overall compliance of terminal aortic circulation under a variety of vascular states induced by injection of vasoactive agents.

Repolarization alternans heterogeneity in healthy subjects and acute myocardial infarction patients

An association between heterogeneity of repolarization alternans (RA) and cardiac electrical instability has been reported. Characterization of RA in health and identification of physiological RA heterogeneity may help discrimination of abnormal RA cases more likely associated to arrhythmic events. Thus, aim of the present study was the identification of a physiological RA region in terms of mean temporal location (MRAD) with respect to the T apex, and mean amplitude (MRAA), by application of our heart-rate adaptive match filter method to clinical ECG recordings from 51 control healthy (CH) subjects and 43 acute myocardial infarction (AMI) patients. Results indicate that RA occurring within the first half of the T wave is dominant in both CH and AMI populations (74.5% and 53.5% of cases, respectively; P<0.05). Definition of physiological RA region in the MRAD vs. MRAA plane (-83 ms ≤ MRAD ≤ 23 ms, 0≤ MRAA ≤ 30 μV) provided 0% and 32.6% abnormal RA cases among the CH subjects and AMI patients, respectively. We conclude that myocardial infarction may associate with an RA occurring early (MRAD<-83 ms) or late (MRAD >23 ms) along the JT segment, in addition or in alternative to an abnormally high RA amplitude (MRAA >30 μV).

Comparison of standard versus orthogonal ECG leads for T-wave alternans identification.

T‐wave alternans (TWA), an electrophysiologic phenomenon associated with ventricular arrhythmias, is usually detected from selected ECG leads. TWA amplitude measured in the 12‐standard and the 3‐orthogonal (vectorcardiographic) leads were compared here to identify which lead system yields a more adequate detection of TWA as a noninvasive marker for cardiac vulnerability to ventricular arrhythmias. Our adaptive match filter (AMF) was applied to exercise ECG tracings from 58 patients with an implanted cardiac defibrillator, 29 of which had ventricular tachycardia or fibrillation during follow‐up (cases), while the remaining 29 were used as controls. Two kinds of TWA indexes were considered, the single‐lead indexes, defined as the mean TWA amplitude over each lead (MTWAA), and lead‐system indexes, defined as the mean and the maximum MTWAA values over the standard leads and over the orthogonal leads. Significantly (P < 0.05) higher TWA in the cases versus controls was identified only occasionally by the single‐lead indexes (odds ratio: 1.0–9.9, sensitivity: 24–76%, specificity: 76–86%), and consistently by the lead‐system indexes (odds ratio: 4.5–8.3, sensitivity: 57–72%, specificity: 76%). The latter indexes also showed a significant correlation (0.65–0.83) between standard and orthogonal leads. Hence, when using the AMF, TWA should be detected in all leads of a system to compute the lead‐system indexes, which provide a more reliable TWA identification than single‐lead indexes, and a better discrimination of patients at increased risk of cardiac instability. The standard and the orthogonal leads can be considered equivalent for TWA identification, so that TWA analysis can be limited to one‐lead system.