L. Brasseur

Diagnostic value of history and maximal exercise electrocardiography in men and women suspected of coronary heart disease.

Coronary arteriographic data have been compared in 278 patients (231 males and 47 females) with the ECG response to a maximal exercise test and with the history (myocardial infarction - MI, typical or atypical angina pectoris - AP). The sensitivity and specificity of exercise ECG were similar in males and females. False negative ECG responses were frequent in males (40%) and false positive ECG responses were frequent in females (38%). This difference between sexes was essentially due in our patients to the higher prevalence of CHD in males (80%) than in females (43%). In the absence of a previous MI, a history of typical AP was associated with coronary heart disease (CHD) in 94% of males and 62% of females. Atypical AP was rarely associated with CHD (18% in males; 11% in females). When typical AP was associated with an abnormal exercise ECG, CHD was highly probable in males (98%) and present in 75% of females. In presence of atypical AP with a normal exercise ECG, CHD was unlikely in males (11%) and in females (8%). We conclude that exercise ECG has limited value for the diagnosis of CHD. In men with typical AP, exercise ECG often confirms the diagnosis but a negative ECG exercise does not rule out CHD because of the high incidence of fales negative responses. In males and females with atypical AP, an abnormal response to exercise is difficult to interpret owing to a high incidence of false positive responses.

Impaired early left ventricular relaxation in coronary artery disease: effects of intracornary nifedipine.

It has been shown that the maximal rate of left ventricular (LV) relaxation is impaired in patients with coronary artery disease (CAD) under basal conditions. To test the hypothesis that this impaired LV relaxation could be related to viable but metabolically abnormal myocardium, we studied the time course of isovolumic LV pressure fall in 21 patients with CAD and in 13 control subjects under basal conditions. This study was repeated after intracoronary injection of the calcium antagonist nifedipine (N) in 11 patients with CAD and in eight controls. Our data showed that isovolumic pressure fall was biexponential in 20 of 21 CAD patients and in six of 13 controls. Moreover, the time constant of isovolumic pressure fall during the first 40 msec after peak (negative) dP/dt (TJ) was significantly greater in CAD patients than in controls (62 ± 3 vs 44 ± 1 msec, p < 0.002); the time constant of pressure fall during the 40-80 msec after peak (negative) dP/dt (T2) was similar in both groups (42 ± 2 vs 39 ± 2 msec, NS). Thirty seconds after injection of nifedipine, T1 and T2 were significantly prolonged in patients with CAD (14 msec and 16 msec, respectively, p < 0.005) and in controls 12 msec and 14 msec, respectively, p < 0.05), and a negative inotropic effect was observed in both groups (peak (positive) dP/dt −16% in controls and −23% in CAD patients, p < 0.01). At rest, impairment of isovolumic relaxation in CAD patients is mainly limited to the first 40 msec after peak (negative) dP/dt, suggesting a dyssynchronous wall motion. This impairment of LV relaxation is better identified by T1 than by peak (negative) dP/dt in individual patients, and cannot be improved by administration of a calcium antagonist.

Alternative diagnostic strategies for coronary artery disease in women: demonstration of the usefulness and efficiency of probability analysis.

Alternative strategies using conditional probability analysis for the diagnosis of coronary artery disease (CAD) were examined in 93 infarct-free women presenting with chest pain. Another group of 42 consecutive female patients was prospectively analyzed. For this latter group, the physician had access to the pretest and posttest probability of CAD before coronary angiography. These 135 women all underwent stress electrocardiographic, thallium scintigraphic, and coronary angiographic examination. The pretest and posttest probabilities of coronary disease were derived from a computerized Bayesian algorithm. Probability estimates were calculated by the four following hypothetical strategies: SO, in which history, including risk factors, was considered; S1, in which history and stress electrocardiographic results were considered; S2, in which history and stress electrocardiographic and stress thallium scintigraphic results were considered; and S3, in which history and stress electrocardiographic results were used, but in which stress scintigraphic results were considered only if the poststress probability of CAD was between 10% and 90%, i.e., if a sufficient level of diagnostic certainty could not be obtained with the electrocardiographic results alone. The strategies were compared with respect to accuracy with the coronary angiogram as the standard. For both groups of women, S2 and S3 were found to be the most accurate in predicting the presence or absence of coronary disease (p less than .05). However, it was found with use of S3 that more than one-third of the thallium scintigrams could have been avoided without loss of accuracy. It was also found that diagnostic catheterization performed to exclude CAD as a diagnosis could have been avoided in half of the patients without loss of accuracy.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary artery reperfusion in acute myocardial infarction: assessment by pre- and postintervention thallium-201 myocardial perfusion imaging.

In a randomized trial of intracoronary streptokinase (STK) therapy in acute myocardial infarction, 44 patients (21 control subjects and 23 patients treated with STK) underwent sequential thallium-201 planar imaging before angiography and after 4 hours (redistribution), 4 days and 6 weeks. Patients were classified according to the presence or absence of angiographic reperfusion of the infarct-related artery. The semiquantitative score of myocardial thallium uptake was expressed as percent of maximal defect score. Both in control and in STK-treated groups, thallium defect scores decreased over time, but this decrease was smaller in the control group (before angiography, 33 +/- 4%; redistribution, 29 +/- 4%; 4 days, 25 +/- 4%; and 6 weeks, 22 +/- 4%) than in the STK group (44 +/- 4%, 38 +/- 4%, 26 +/- 4% and 21 +/- 3%, respectively). In patients in whom reperfusion was achieved (20 STK-treated, 6 control subjects), a marked decrease in thallium score was observed (before angiography, 40 +/- 4%; redistribution, 32 +/- 4%; 4 days, 20 +/- 5%; and 6 weeks, 14 +/- 22%) compared with patients in whom reperfusion was not achieved (37 +/- 4%, 36 +/- 5%, 33 +/- 5% and 33 +/- 4%, respectively). These results indicate that serial thallium imaging is an accurate method of assessing changes in myocardial perfusion after acute myocardial infarction. Restoration of thallium uptake was observed after reperfusion of the infarct-related artery whether this recanalization was seen spontaneously or after successful thrombolysis.

Hemodynamic Determinants of Exercise ST-Segment Depression in Coronary Patients

Eight patients with coronary heart disease were studied during two periods of exercise separated by 30 min of rest; workload was increased in a stepwise fashion every minute of exercise up to a level that produced limiting symptoms of angina, fatigue, or dyspnea. The magnitude of ST-segment depression and the central aortic pressure were measured during exercise and recovery periods, and myocardial oxygen requirements were estimated by the pressure-time index (systolic aortic pressure × heart rate × ejection time).Seven of the eight patients exhibited a close relationship (r ranged from 0.74 to 0.98) between magnitude of exercise ST-segment depression and indices expressing myocardial oxygen requirements; heart rate, blood pressure, and ejection time were also related to magnitude of exercise ST-segment depression. These relationships were reproducible during two consecutive exercises. Like onset of angina, magnitude of exercise ST-segment depression is usually related to hemodynamic factors influencing myocardial oxygen needs. Consequently, comparisons of exercise-induced ST depression before and after therapy (drugs, physical training, and surgery) are valid only if ECG findings are compared at the same level of myocardial oxygen requirements.In contrast, absence of such a relationship during recovery suggests an important difference in mechanisms of the post-exercise electrocardiogram.

Force-velocity-length relations in hypertrophic cardiomyopathy: Evidence of normal or depressed myocardial contractility

To assess myocardial contractility in patients with hypertrophic cardiomyopathy (HC), force-velocity-length relations were analyzed during left ventricular (LV) ejection. LV pressure, volume and wall stress data in 15 patients with HC were analyzed and compared with values from 32 normal subjects. Patients with HC had a greater LV mass than did normal subjects (272 versus 96 g/m2, p less than 0.001), elevated LV end-diastolic pressure (17.5 versus 9.8 mm Hg, p less than 0.01) and impaired LV relaxation compared with those of normal subjects. Patients with HC also had a greater ejection fraction (84 +/- 7 versus 74 +/- 8%, p less than 0.01) and mean velocity of shortening than did normal subjects. However, in patients with HC, end-systolic stress (60 +/- 29 versus 187 +/- 61 kdyne/cm2, p less than 0.001) was significantly lower. End-systolic volume and stress data were linearly related in normal subjects (r = 0.88), and values from patients with HC fell either within the lowest part of the 95% confidence interval of this normal relation or outside it in the zone of depressed contractility (11 patients with HC). In addition, the slopes of the relations between end-systolic wall stress and ejection fraction or mean velocity of shortening were abnormal in patients with HC; the slope of the stress-volume trajectory during late ejection was also depressed in 12 patients with HC (average slope 2.6 versus 5.5 kdyne/cm5/m2, p less than 0.001). Thus, there is no evidence of a hypercontractile state in patients with HC; their high values of ejection phase indexes may be explained by a reduction in myocardial afterload.

Relationship between changes in left ventricular inotropic state and relaxation in normal subjects and in patients with coronary artery disease.

The aim of the study was to examine the changes in left ventricular (LV) relaxation rate induced by variations in inotropic state. Eight normal subjects and 29 patients with coronary artery disease (CAD) were studied. First, we used interventions that increase myocardial calcium influx (atrial pacing or postpacing beat) or decrease it (intracoronary injection of nifedipine). Relaxation rate was estimated from the time constant (T1) of isovolumic LV pressure fall during the first 40 msec after peak negative dP/dt. Under basal conditions, T1 was impaired in CAD patients (58 vs 43 msec; p < 0.01), despite similar heart rate, LV pressures and peak positive dP/dt (1620 vs 1787 mm Hg/sec; NS). During atrial pacing at 135 ± 7 beats/mm, peak positive dP/dt increased to 2220 mm Hg/sec in 11 CAD patients and to 2256 mm Hg/sec in eight normal subjects. T1 decreased more in CAD patients than in normal subjects (17 vs 7 msec; p < 0.01). T1 changes also differed in the postpacing beat between CAD patients and normal subjects (−6 vs 5 msec; p < 0.01) or when nifedipine was injected during the pacing (4 vs 20 msec; p < 0.01). Intravenous calcium injection during atrial pacing in another group of 18 CAD patients further improved peak positive dP/dt and T1 (−3 msec; p < 0.05) and normalized the changes in relaxation during the postpacing beat. Our data indicate that a variable coupling between LV inotropic state and relaxation rate exists in man during changes in calcium influx and that this coupling is abnormal in CAD patients.

Hemodynamic Determinants of Maximal Oxygen Intake in Patients with Healed Myocardial Infarction: Influence of Physical Training

Fourteen patients with a healed myocardial infarction (no angina pectoris) had maximal oxygen intake (VO2 max) determinations and hemodynamic studies at submaximal and maximal exercise levels; seven patients were studied two months after an acute myocardial infarction (untrained group) while seven had followed a physical training program for 13.5 months (trained group). At the maximal exercise level, all patients exhibited a fall in stroke volume which was 15% (untrained group) and 18% (trained group) lower than at submaximal exercise level: this decrease in stroke volume, presumably resulting from myocardial ischemia, was the major factor limiting the Vo2 max of the patients. The maximal arteriovenous oxygen (A-VO2) difference of untrained patients was the same (14.4 ml/100 ml) as for healthy subjects.Higher VO2 max of trained patients (2.50 vs 2.07 liters/min) resulted almost exclusively from greater maximal A-VO2 difference (16.5 vs 14.4 ml/100 ml); this suggests that long-term physical training increases peripheral extraction of oxygen by the working muscles.

Antianginal Effects of Corwin, a New Beta-adrenoceptor Partial Agonist

The hemodynamic effects of corwin were evaluated in 9 patients with coronary artery disease and without clinical signs of heart failure at rest, during submaximal exercise and during exercise-induced angina pectoris before and after administration of corwin. Angina pectoris was always prevented after the drug was given and the exercise intensity was increased until recurrence of angina pectoris; hemodynamic data were also recorded at this higher exercise capacity (+16%: p less than 0.001). At rest, corwin increased heart rate (from 80 to 84 beats/min) and pressure-rate product. During submaximal exercise, heart rate decreased from 105 to 96 beats/min, and pressure-rate product and ST-segment depression also decreased after corwin. The prevention of angina pectoris in all patients was accompanied by a lower heart rate (from 132 to 117 beats/min), pressure-rate product and ST-segment depression. At rest and during exercise, the cardiac output was unchanged and the pulmonary capillary wedge pressure was slightly decreased after corwin (from 12.5 to 10 mm Hg; p less than 0.001). At the 16% greater exercise capacity after corwin, angina pectoris recurred at the same values of cardiac output, pulmonary wedge pressure and ST-segment depression; maximal heart rate decreased from 132 to 124 beats/min, and the pressure-rate product was lower. Thus, corwin is an active antianginal drug. Its effects are likely due to a decrease in pressure-rate product and myocardial oxygen requirements during exercise. In contrast to beta-antagonists devoid of partial agonist activity, corwin does not depress left ventricular function either at rest or during exercise.

Hemodynamic-effects of Molsidomine At Rest and During Submaximal and Maximal Exercise in Patients With Coronary-artery Disease Limited By Exertional Angina-pectoris

To analyze the mechanisms of action of molsidomine, a new antianginal drug, 10 patients with coronary artery disease and exertional angina pectoris were studied. Hemodynamic measurements were made at rest, during submaximal exercise and during angina-limited exercise before and 1 hour after intravenous administration of 2 mg of molsidomine. When angina pectoris was prevented after the drug was given (6 of 10 patients), the exercise intensity was increased until the recurrence of angina (3 patients) or until exhaustion (3 patients), and hemodynamic data were recorded at this higher exercise capacity. At rest and during submaximal exercise, molsidomine increased heart rate and decreased cardiac output and mean systemic and pulmonary arterial pressures. The prevention of angina pectoris was attended by lower mean systemic and pulmonary arterial pressures and pressure-rate product; cardiac output and heart rate were unchanged. The greater exercise capacity (+26 percent) after molsidomine was attended by increases in maximal cardiac output (+19 percent) and in arteriovenous oxygen difference (+6 percent); the maximal pressure-rate product was unchanged and systemic vascular resistance was lower. The mechanisms of action of molsidomine are very similar to those of nitrates and imply a decrease in venous and arterial tone. Molsidomine deserves further study in patients with angina or congestive heart failure.