Jos L. Willems

Significance of initial ST segment elevation and depression for the management of thrombolytic therapy in acute myocardial infarction. European Cooperative Study Group for Recombinant Tissue-Type Plasminogen Activator.

To determine the ability of initial ST segment elevation and depression to predict infarct size limitation by thrombolytic therapy, data were analyzed in 721 patients with acute myocardial infarction who were admitted to a randomized, placebo-controlled study of intravenous recombinant tissue-type plasminogen activator. Patients with QRS duration of 120 msec or more or with previous history of myocardial infarction were excluded, leaving 322 in the treatment and 333 in the placebo group. Cumulative 72-hour release of alpha-hydroxybutyrate dehydrogenase and global ejection fraction as well as left ventricular wall motion derived from angiography were used as independent measures of infarct size. Electrocardiograms obtained at admission, 6 hours after start of therapy, and before discharge were analyzed. All ST measurements were made by hand at the J point and 60 msec after the J point. Patients with high ST segment elevation at admission (i.e., sum of ST elevation at 60 msec after the J point was 20 mm or more) had significantly larger infarction and higher hospital mortality when compared with those with lower (less than 20 mm) ST elevation. Reciprocal ST segment depression also showed a linear relation with infarct size and mortality, independent from ST elevation, both in anterior and inferior myocardial infarction. The sum of deviations measured at the J point and 60 msec after the J point differed significantly, especially in anterior myocardial infarction at admission (mean, 16 +/- 9 versus 23 +/- 11 mm). The prognostic value of one measurement was not, however, superior over the other. Treatment with recombinant tissue-type plasminogen activator was most effective in those with large ST deviations at admission, but patients with anterior infarction and smaller ST shifts also appeared to benefit from therapy. Results in individual patients were variable, and the overall correlation of initial ST shifts with enzymatic infarct size was rather low. In conclusion, the present study shows that the magnitude of initial ST elevation and also of reciprocal ST depression in the admission electrocardiogram is valuable for the management and assessment of thrombolytic therapy in patients with acute myocardial infarction.

A reference data base for multilead electrocardiographic computer measurement programs

In an effort to standardize and evaluate the performance of electrocardiographic computer measurement programs, a 15 lead reference library has been developed based on simultaneously recorded standard 12 lead and orthogonal XYZ lead data. A set of 250 electrocardiograms (ECGs) with selected abnormalities was analyzed by a group of five referee cardiologists and 11 different 12 lead and 6 XYZ computer programs. Attention was focused on the exact determination of the onsets and offsets of P, QRS and T waves. The referees performed their task on highly amplified, selected complexes from the library in a two round process. Median results of the referees coincided best with the median derived from all programs. An analysis of stability proved that the combined program median was a robust reference. However, some individual program results were widely divergent. Paired t tests demonstrated earlier onset for P and QRS (p less than 0.001), as well as later offset for P and T waves in the median 12 lead than in the XYZ results. Significant differences also existed among results obtained by programs analyzing all standard ECG leads at one time, the so-called multilead programs, and those obtained by the conventional standard three lead analysis programs. As a consequence, the derived P, PR, QRS and QT interval measurements varied quite widely among the various programs. Significant differences were also observed among measurements of Q, R and S duration. Some programs showed Q waves that were on the average 6 ms (p less than 0.001) longer than those of others. This may significantly influence diagnostic performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of the performance of electrocardiographic computer programs with the use of a reference data base.

To allow an exchange of measurements and criteria between different electrocardiographic (ECG) computer programs, an international cooperative project has been initiated aimed at standardization of computer-derived ECG measurements. To this end an ECG reference library of 250 ECGs with selected abnormalities was established and a comprehensive reviewing scheme was devised for the visual determination of the onsets and offsets of P, QRS, and T waves. This task was performed by a group of cardiologists on highly amplified, selected complexes from the library of ECGs. With use of a modified Delphi approach, individual outlying point estimates were eliminated in four successive rounds. In this way final referee estimates were obtained that proved to be highly reproducible and precise. This reference data base was used to study measurement results obtained with nine vectorcardiographic and 10 standard 12-lead ECG analysis programs. The medians of program determinations of P, QRS, and T wave onsets and offsets were close to the final referee estimates. However, an important variability could be demonstrated between measurements from individual programs and mean differences from the referee estimates amounted to 10 msec for QRS for certain programs. In addition, the variances of all programs with respect to the referee point estimates were variable. Some programs proved to be more accurate and stable when the data from high- vs low-noise recordings were analyzed. Average Q wave durations calculated from ECGs for which programs agreed on the presence of a Q or QS wave differed by more than 8 msec in several program-to-program comparisons. Such differences may have important consequences with respect to diagnostic performance. Various factors that might explain these differences have been determined. The present study demonstrates that to allow an exchange of results and diagnostic criteria between different ECG computer programs, definitions, minimum wave requirements, and measurement procedures urgently need to be standardized.

An Enquiry into the Role of Cobalt in the Heart Disease of Chronic Beer Drinkers

The natural history of a new disease entity in chronic beer drinkers consisting of pericardial effusion, a low cardiac output, and in about half of the cases of polycythemia is presented. Normalization of the heart volume, the hemoglobin value, and the hemodynamic state was obtained in patients who stopped drinking. Further evidence of the importance of cobalt in the development of the disease is presented. All patients drank beer to which cobalt was added and the disease was not seen in chronic alcoholics drinking wine or other alcoholic beverages. In view of the rather small quantity of cobalt consumed, an hypothesis is formulated which attributes the cobalt toxicity in chronic alcoholics, to a dietary deficiency of sulfhydryl-groups containing amino acids and a dietary deficiency of protein.

Frequency of angina pectoris and coronary artery disease in severe isolated valvular aortic stenosis

A consecutive series of 192 patients (121 men and 71 women, mean age 59 years, range 28 to 82) with isolated, severe valvular aortic stenosis was with isolated, severe valvular aortic stenosis was analyzed retrospectively to determine the relation of angina pectoris and coronary risk factors to angiographically significant coronary artery disease (CAD). Significant CAD (diameter reduction greater than or equal to 50%) was found in 47 patients (24%). Angina was present in 83% of them, but it was also found in 61% of the non-CAD patients. This symptom had as a result a low positive predictive value (31%). Of the patients without angina (n = 65) 12% had significant CAD. The negative predictive value of angina alone was thus 88%. By using multivariate logistic regression, a risk score could be calculated based on angina, age and sex, which increased the negative predictive value to 95%. It was concluded that coronary arteriography can only be omitted in severe aortic valvular stenosis, when patients have no angina and when they are less than 40 years of age for men and less than 50 years for women. For all other cases, coronary arteriography should be recommended.

Angiotensin-converting enzyme inhibition with fosinopril sodium in the prevention of restenosis after coronary angioplasty.

BACKGROUND Several angiotensin-converting enzyme inhibitors have antiproliferative effects in a rat model after carotid artery balloon injury. METHODS AND RESULTS We conducted a randomized, double-blind, placebo-controlled trial to assess the effect of fosinopril, a novel angiotensin-converting enzyme inhibitor, in restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA). Patients received fosinopril or matched placebo 10 mg at least 18 hours before PTCA, 20 mg at least 4 hours before PTCA, and 40 mg daily for 6 months. In addition, all patients received aspirin. Coronary angiograms before PTCA and immediately after PTCA as well as at 6-month follow-up were quantitatively analyzed. A total of 509 patients were recruited. The final per-protocol population consisted of 153 fosinopril-treated and 151 placebo-treated patients. Restenosis rates according to the National Heart, Lung, and Blood Institute criterion 4 (loss of > or = 50% of the initial gain [primary end point]) were 45.7% and 40.7% in the fosinopril and control groups, respectively (not significant). The respective mean differences in minimal coronary luminal diameter between post-PTCA and follow-up angiograms were -0.59 +/- 0.71 mm and -0.51 +/- 0.67 mm (not significant). Clinical events during the 6-month follow-up period, analyzed on an on-treatment basis, were ranked according to the most serious event. The respective numbers in the fosinopril and the control groups were for death, 0 and 0; myocardial infarction, 0 and 0; coronary artery bypass graft surgery, 1 and 3; repeat PTCA, 35 and 35; recurrent signs of ischemia necessitating early repeat coronary angiography and managed medically, 6 and 7; and none of the above, 111 and 106. All these differences were significant. CONCLUSIONS Administration of fosinopril in a dose of 40 mg daily during 6 months after PTCA does not prevent restenosis and has no effect on overall clinical outcome.

Common standards for quantitative electrocardiography

A large international co-operative project, sponsored by the European Commission, was launched in 1980 aimed at developing common standards for quantitative electrocardiography. The first and main objective of the project was to reduce the wide variation in wave measurements currently obtained by electrocardiographic computer programs. To this end a reference library was developed and a comprehensive reviewing scheme was devised for the visual determination of the onsets and offsets of P, QRS and T. This task was performed by a board of cardiologists on highly amplified recordings, in an interactive four round Delphi-type analysis. The reference library, so obtained, has become an internationally recognized yardstick for the evaluation and improvement of ECG measurement programs. It has been used to test the performance of 9 VCG and 10 standard 12-lead programs. The library proved to be a useful instrument in the establishment of recommendations for more precise measurement rules and definitions. Records with added noise and multi-lead ECGs were subsequently analysed to meet specific objectives. The project was expanded in 1984 towards testing and improvement of diagnostic criteria and classification programs.

The Left Ventricular Ejection Time in Elderly Subjects

The left ventricular ejection time (LVET) was studied by means of the carotid artery tracing in 512 elderly subjects (205 male and 307 female) who were between 60 and 90 years old (mean age, 70.5 years). A highly significant correlation was found between heart rate (HR) and LVET. The data on these aged subjects were compared and analyzed with the results previously reported concerning young and middle-aged adults. A small but significant increase of LVET with aging, independent of changes in HR and blood pressure, could be demonstrated by multiple regression analysis. A statistically significant difference existed between the sexes. The influence on LVET of parameters other than HR was small.

Diastolic properties of the left ventricle in normal adults and in patients with third heart sounds.

To explore the pathogenesis of the third heart sound (S3), left ventricular hemodynamics in early diastole were studied during catheterization in normal adults without S3S (group I, n = 12) and in cardiac patients with S3S as the result of severe mitral regurgitation (group II, n = 11), dilated cardiomyopathy (group III, n = 24) or restricted left ventricular filling (group IV, n = 4). The height and steepness of the rise in left ventricular pressure after minimum diastolic pressure (the so-called rapid filling wave), maximum dV/dt, and the time constant of fall in isovolumetric pressure were measured. The completeness of relaxation was evaluated from the number of time constants elapsed at the time of minimum diastolic pressure. Pressure-volume data were fitted to simple elastic and viscoelastic models incorporating inflow rate into the equation. In all patients with S3S a significantly higher and steeper rapid filling wave was found than in normal adults. Maximum dV/dt was significantly greater in group II (1084.9 +/- 416 ml/sec; mean +/- SD) than in the other groups (463.9 +/- 177.1 ml/sec in group I, 448.8 +/- 134.0 ml/sec in group III, and 709.9 +/- 226.8 ml/sec in group IV). No significant differences in left ventricular chamber elastic properties in the different groups were found. However, intrapatient comparisons of the results of the use of elastic and viscoelastic equations revealed a significantly better curve fit (r = .930 vs .968, p less than .005) and a much higher viscous constant for group III. Similar results were found in group IV.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of the classification ability of the electrocardiogram and vectorcardiogram

Controversy exists over the classification ability of the standard 12-lead electrocardiogram (EGG) and the vectorcardiogram (VCG). In this study the diagnostic information content and classification performance of the ECG and VCG were examined using multivariate statistical techniques and a large validated data base of 3,266 cases. Logistic classification models were developed to differentiate between 7 diagnostic entities: normal (n = 538), left (n = 557), right (n = 323) and biventricular (n = 437) hypertrophy, and anterior (n = 390), inferior (n = 657) and combined (n = 364) myocardial infarction. The models were obtained from a learning sample (n = 2,446) using an optimal set of computer derived ECG and VCG measurements. They were subsequently applied to a test sample (n = 820). In the learning sample, the discrimination models resulted in a total correct classification rate of 69.6% for the ECG and 69.4% for the VCG. The total accuracy rate was slightly lower in the test set: 66.3% for the ECG and 67.1% for the VCG. The combined use of the best ECG and VCG variables did not increase total diagnostic accuracy. When cases with biventricular hypertrophy and combined infarction were deleted, accuracy rates of more than 80% were achieved for both lead systems. Differences in the classification rates for the subgroups were not statistically significant. Thus, the conventional 12-lead ECG is as good as the VCG for the differential diagnosis of 7 main entities, provided identical procedures are used in the design of the classifiers.(ABSTRACT TRUNCATED AT 250 WORDS)