Christian Brohet

LDL-C goal attainment with the addition of ezetimibe to on-going simvastatin treatment in coronary heart disease patients with hypercholesterolemia

ABSTRACT Objective: To evaluate the addition of ezetimibe or placebo to on-going simvastatin treatment on attaining the LDL‐C treatment target of ≤ 2.60 mmol/L (100 mg/dL) in coronary heart disease (CHD) patients with hypercholesterolemia. Methods: Patients with documented CHD were recruited if they were on a stable dose of simvastatin 10 mg or 20 mg for at least 6 weeks, had LDL‐C > 2.60 mmol/L and ≤ 4.20 mmol/L (> 100 mg/dL and ≤ 160 mg/dL), triglycerides ≤ 4.00 mmol/L (355 mg/dL) and hepatic transaminases and creatine kinase ≤ 50% above the upper limit of normal. After a 4-week placebo and diet run-in period, eligible patients were randomized to a double-blind, placebo-controlled comparative study with ezetimibe 10 mg co-administered with on-going simvastatin 10 mg or 20 mg (n = 208) versus placebo to match ezetimibe co-administered with simvastatin 10 mg or 20 mg for 6 weeks (n = 210). Results: When ezetimibe was added to on-going simvastatin therapy, a significantly greater percentage of patients attained the LDL‐C target of ≤ 2.60 mmol/L after 6 weeks of treatment compared to placebo added to on-going simvastatin (80.4% vs. 17.4%, respectively; p ≤ 0.001). When co-administered with on-going simvastatin therapy, mean percentage reduction in LDL‐C from baseline was significantly larger in the ezetimibe group compared to placebo (27.1% vs. 4.1%, respectively; p ≤ 0.001). The co-administration of ezetimibe or placebo to on-going simvastatin treatment was generally well tolerated. Conclusions: Ezetimibe co-administered with on-going simvastatin 10 mg or 20 mg treatment enabled more CHD patients with hypercholesterolemia to attain the LDL‐C treatment target of ≤ 2.60 mmol/L.

Dispersion of ventricular repolarisation: a marker of ventricular arrhythmias in patients with previous myocardial infarction

Objective To examine whether, in coronary patients after myocardial infarction, the dispersion of ventricular repolarisation measured through QT and JT intervals from a surface electrocardiogram could allow separation of those with ventricular tachyarrhythmias (VT) complicating their myocardial infarct from those without. Design A retrospective comparative study. Setting University hospital. Patients 39 patients with myocardial infarction complicated by VT, 300 patients after myocardial infarction without arrhythmic events, and 1000 normal subjects. The myocardial infarction groups were divided into anterior, inferior, and mixed locations. Interventions A computer algorithm examined an averaged cycle from a 10 second record of 15 simultaneous leads (12 lead ECG + Frank XYZ leads). After interactive editing, four intervals were computed: QTapex, JTapex, QTend, and JTend. For each interval, the dispersion was defined as the difference between the maximum and minimum values across the 15 leads. Results The mean values of all four dispersion indices were higher in patients with myocardial infarction than in normal subjects (p < 0.01). In the infarct groups, patients with VT had significantly greater mean and centile dispersion values than those without VT. For instance, the 97.5th centile value of QTend was 65 ms in normal individuals, 90 ms in infarct patients without arrhythmia, and 128 ms in those with VT; 70% of the infarct patients who developed serious ventricular arrhythmias had values exceeding the 97.5th centile of the normal group, while only 18% of the infarct patients without arrhythmia had dispersion values above this normal upper limit. Among the infarct patients, nearly half of those (18 of 39) with tachyarrhythmias had dispersion values that exceeded the 97.5th centile of those without arrhythmia. Conclusions Dispersion of ventricular repolarisation may be a good non-invasive tool for discriminating coronary patients susceptible to VT from those who are at low risk.

Possibilities of using neural networks for ECG classification

Some characteristics of the neural network approach have been tested and validated for the particular problem of diagnostic classification in the field of computerized electrocardiography. Two different databases have been used for the evaluation process: CORDA, developed by the Medical Informatics Department of the University of Leuven, and ECG-UCL, developed by the Cliniques Universitaires Saint-Luc, Université Catholique de Louvain. Electrocardiographic signals classified on the basis of electrocardiographic independent clinical data, with a single diagnosis and no conduction abnormalities, have been considered. Seven diagnostic classes have been taken into account, including the different locations of ventricular hypertrophy and myocardial infarction. Two architectures of neural networks have been analyzed in detail considering three aspects: the normalization process, pruning techniques, and fuzzy preprocessing by the use of radial basis functions. The comparison of the results obtained with the two databases will be discussed in detail.

Dispersion of ventricular repolarization in hypertrophic cardiomyopathy

On an averaged QRS-T cycle from a 15-lead record (12-lead electrocardiogram + XYZ leads) and through interactive editing, four electrocardiographic indices of the dispersion of ventricular repolarization (DVR) are automatically computed and represent the maximal interlead difference of QT and JTend and QT and JTapex. The values of these indices were then examined in three clinical groups matched for age and sex: normal subjects (control), patients with left ventricular hypertrophy (LVH group), and patients with hypertrophic cardiomyopathy (HCM group) without ventricular arrhythmias and without interacting drugs. The mean values of all four DVR indices were significantly increased in the HCM group compared with the control group and the LVH group of another origin (ie, for the QTe dispersion index, the mean values and the 97.5th percentiles were, respectively, 65 +/- 18 ms and 97 ms in the HCM group, 41 +/- 25 ms and 79 ms in the LVH group, and 31 +/- 15 ms and 58 ms in the control group). The maximal QT interval was also significantly longer in the HCM group (464 +/- 30 ms) than in the LVH group (436 +/- 32 ms) and the control group (428 +/- 25 ms).

Amiodarone-induced thyrotoxicosis suggestive of thyroid damage

Amiodarone-induced thyrotoxicosis (AIT) is generally believed to result from increased hormonal synthesis related to the iodine overload. Thyroid damage has recently been incriminated as a pathophysiological mechanism. We report 3 cases of AIT associated with clinical and/or biochemical features consistent with thyroid damage. This hypothesis was supported by a painful thyroid (case 1 ), transient high serum Tg (case 2), a transient (case 2) or persistent (case 3) hypothyroid phase and an undetectable technetium thyroid uptake during the hypothyroid period (case 3). These clinical observations support the previous histological data indicating that thyroid follicular disruption might contribute to the pathogenesis of AIT.

Computer-assisted Study of ECG Indices of the Dispersion of Ventricular Repolarization

A new computer-assisted method for the quantitative assessment of the dispersion of ventricular repolarization (DVR) has been developed. Through interactive editing of an averaged QRS-T cycle from a 15-lead electrocardiographic (ECG) record (12-lead ECG + XYZ leads), five ECG indices of DVR are automatically computed: they represent the maximal interlead difference of QT and the intervals from the J point to the T wave end, from the J point to the T wave apex, and from the T wave apex to the T wave end. The standard limits of these indices were then established in six clinical groups, including normal subjects and patients with left ventricular hypertrophy, with myocardial infarction, and with intraventricular conduction defect, all subjects being without ventricular arrhythmias and without interacting drugs. The mean values and percentile ranges of all DVR indices were lower in the normal group than in all pathologic groups. The 97.5th percentiles of the QT end dispersion and the JT end dispersion were, respectively, 65 and 76 ms in normal subjects, 84 and 86 ms in patients with inferior MI; 89 and 100 ms in those with anterior MI; 90 and 98 ms in those with left ventricular hypertrophy; and 94 and 99 ms in those with intraventricular conduction defects. This suggests that increased DVR is associated with the varieties of heart disease represented in this study, even in the absence of ventricular arrhythmias, and also that individual measurements of DVR used as predictors of future arrhythmic events should be referred to the standard range of their own clinical group.

Quantative analysis of the vectorcardiogram in obesity. The effects of weight reduction

Vectorcardiograms (VCG) recorded in 37 subjects with marked chronic EXOGENOUS OBESITY (AVERAGE WEIGHT: 285 LBS.) WERE COMPARED before and after a significant weight reduction (average weight loss: 86 lbs). They were also compared with the VCGs of 293 age and sex matched controls with normal body weight. The SVEC III corrected orthogonal lead system was used, and out of several hundred vectorcardiographic measurements obtained by computer processing, 59 measurements representing various scalar, planar and spatial voltage and angular measurements were selected for study and comparisons. No significant differences were found between the measurements of obese subjects and those of the controls. Of 59 VCG measurements, 13 showed significant differences after weight reduction (paired t test) although they remained within the range of normal controls. There was a trend toward decrease of P and QRS amplitudes after weight reduction. There were no significant changes in the angular measurements. Although they are statistically significant these changes in voltage are too small to be detected in clinical vectorcardiography. The possible decrease of a preexisting myocardial hypertrophy superimposed onto the changes in the anatomy of the thorax might explain the effects of weight reduction. In general the reproducibility of VCG measurements obtained by the SVEC III system was greater than that reported in day-to-day operation with the Frank system in normal subjects.

The prognostic accuracy of different QT interval measures.

Background: The QT intervals accuracy for predicting arrhvthmic death varies between studies, possibly due to differences in the selection of the lead used for measurement of the QT interval. The purpose of this study was to analyze the prognostic accuracy of all known ways to select the lead.

Computer interpretation of pediatric orthogonal electrocardiograms: statistical and deterministic classification methods.

Statistical multivariate and conventional deterministic methods of computerized interpretation of the electrocardiogram (ECG) were compared in the analysis of 1711 pediatric orthogonal ECGs validated by nonelectrocardiographic criteria on the basis of clinical and anatomic diagnoses. Among 642 children catheterized for the evaluation of congenital heart disease, there were 140 patients with left ventricular hypertrophy, 299 with right ventricular hypertrophy, and 203 with biventricular hypertrophy. A group of 1069 obviously healthy school children was studied as a control. The overall accuracy of multigroup ECG diagnosis was 85% and 79% for the statistical and deterministic methods, respectively. The diagnostic performances of both methods expressed in terms of sensitivity and predictive value were the highest for normal children and those with right ventricular hypertrophy and lowest for children with biventricular hypertrophy. The statistical method was more sensitive in the diagnosis of left ventricular hypertrophy (74% vs 64%), right ventricular hypertrophy (86% vs 83%), and biventricular hypertrophy (62% vs 50%). Mutual agreement for a correct diagnosis by the two methods was 83% for normal children and 82% for those with right ventricular hypertrophy but only 61% for children with left ventricular hypertrophy and 39% for those with biventricular hypertrophy. In conclusion, better classification results are obtained with statistical multivariate techniques as compared with conventional deterministic analysis, but both methods of ECG interpretation are complementary and their combination in the same electrocardiographic computer program can improve diagnostic accuracy.

Autologous blood donation before myocardial revascularization: a Holter-electrocardiographic analysis.

The influence of preoperative autologous blood donation on myocardial ischemia and arrhythmias was evaluated in 24 patients scheduled for coronary artery bypass grafting (CABG). All had a Holter recorder placed 24 hours before predonation (day 1), the cassette was changed prior to donation, and the recording continued for 24 hours thereafter (day 2). Each patient served as his or her own control, and observations made on day 2 were compared with those of day 1. Ischemia was quantitated by calculating the duration (C.Dur.) and the area (C. Area) of ischemic ST segment depressions, and ventricular premature beats (VPB) were classified according to the Lown grading system. Twenty-one men and 3 women were monitored. On day 1, 9 patients had 20 ischemic events, 3 being symptomatic. Nine patients demonstrated ischemia on day 2, representing a total of 3 symptomatic and 26 silent events. When comparing the two monitoring periods, 7 patients had longer or more severe ST segment depression whereas 6 other patients presented with more severe VPBs on day 2. Three patients had less ischemia on day 2, one remained stable, and 13 had no ischemia throughout the study. Silent ischemia was significantly more prolonged (C.Dur.Sil 316 v 152 sec, P < 0.05) and more intense (C. Area Sil 8 v 3.8 mm.min, P < 0.05) on day 2. Moreover, on top of a normal circadian distribution of ischemic events in the morning and in the evening, 40% of events were related to the donation or to a trip to the hospital. No preoperative characteristic helped to detect patients at risk.(ABSTRACT TRUNCATED AT 250 WORDS)