Antonio Mussini

Coronary arterial spasm as a cause of exercise-induced ST-segment elevation in patients with variant angina.

Four patients with variant angina pectoris exhibited reproducible exercise-induced chest pain ST-segment elevation. Coronary arterial spasm was documented with arteriography during exerciseinduced ST-segment elevation (three patients) or after intravenous administration of ergonovine maleate (one patient). Our observations show that in patients with variant angina exercise can trigger coronary arterial spasm, thus inducing anginal pain ST-segment elevation.

Coronary atherosclerotic plaques with and without thrombus in ischemic heart syndromes: A morphologic, immunohistochemical, and biochemical study

We investigated incidence, severity, and distribution of coronary atherosclerosis, acute thrombosis, and plaque fissuring in ischemic heart disease (both unstable-acute syndromes and chronic ischemia) and in nonischemic controls. We also studied the structural, immunohistochemical, and biochemical profile of plaques, with and without thrombus, including morphometry, immunophenotyping of inflammatory infiltrates, cytokine presence, and ultrastructural features. Critical coronary stenosis was almost the rule in both acute and chronic ischemic series (greater than 90%) whereas it reached 50% in control subjects. Thrombosis was principally characteristic of unstable-acute ischemic syndromes (unstable angina, 32%; acute myocardial infarction, 52%; cardiac sudden death, 26%) but was also found in chronic ischemia (stable angina, 12%; ischemic cardiomyopathy, 14%) and in control subjects (4%). Plaque fissuring without thrombus occurred in low percentages in lipid-rich, severe eccentric plaques in most series. Major differences were found between pultaceous-rich versus fibrous plaques rather than between plaques with or without thrombus. Pultaceous-rich plaques were frequent in sites of critical stenosis, thrombosis, and ulceration. Inflammatory infiltrates, i.e., T cells, macrophages, and a few beta cells, mostly occurred in lipid-rich, plaques unrelated to thrombus. In adventitia, infiltrates were a common finding unrelated to any syndrome. Necrotizing cytokines such as alpha-TNF were immunohistochemically detected in macrophages, smooth muscle, and intimal cells and detected by immunoblotting in 67% of pultaceous-rich plaques, either with or without thrombus. Immune response mediators such as IL-2 were also expressed in analogous plaques but in a minor percentage (50%-40%). Media were extensively damaged in severely diseased vessels with and without thrombus. Ultrastructural study showed that the fibrous cap was either highly cellular or densely fibrillar. Intimal injury with collagen exposure was often associated with platelet adhesion, whereas foamy cell exposure was not. In conclusion, investigated parameters were essentially similar in plaques, both with and without thrombus, whereas major differences were found between pultaceous-rich and fibrous plaques. Since platelets adhere to exposed collagen and not to foam cells, the type of exposed substrates could play a major role in thrombosis.

Comparison of Dobutamine Stress Echocardiography, Dipyridamole Stress Echocardiography and Exercise Stress Testing for Diagnosis of Coronary Artery Disease

To compare the value of dobutamine and dipyridamole stress echocardiography with exercise stress testing for the diagnosis of coronary artery disease (CAD), 80 patients with chest pain of suspected myocardial ischemic origin (57 with CAD and 23 without significant CAD) underwent dobutamine stress echocardiography (5 to 40 micrograms/kg/min), dipyridamole echocardiography (0.84 mg/kg over 10 minutes) and bicycle exercise electrocardiography after discontinuation of antianginal treatment. Dobutamine echocardiography and exercise testing revealed a higher overall sensitivity than dipyridamole echocardiography (79 vs 60%, p < 0.005; 77 vs 60%, p < 0.05, respectively); this finding was due to a higher dobutamine and exercise sensitivity in 1-vessel CAD (62 vs 33%, p < 0.05 for both tests), whereas sensitivity of the 3 tests was similar in multivessel CAD. Dobutamine and dipyridamole showed a higher specificity than exercise (83 vs 43%, p < 0.01; 96 vs 43%, p < 0.005, respectively). Diagnostic accuracy of dobutamine echocardiography was higher than that of exercise (80 vs 67%, p < 0.05), whereas the difference with dipyridamole (80 vs 70%) was not significant. In the tests that yielded positive results, double product during exercise was significantly higher than that during dobutamine and dipyridamole echocardiography. No major complications occurred during the tests, but adverse effects were more frequent during dobutamine testing. Thus, dobutamine echocardiography may be superior to dipyridamole echocardiography and exercise electrocardiography for the diagnosis of CAD.

Dobutamine stress echocardiography for assessment of myocardial viability and ischemia in acute myocardial infarction treated with thrombolysis

To evaluate the role of dobutamine echocardiography for early assessment of myocardial viability and ischemia in acute myocardial infarction (MI), 59 patients with thrombolyzed acute MI underwent low- (5-10 micrograms/kg/min, 8 patients) and high-dose (20-40 micrograms/kg/min, 51 patients) dobutamine echocardiography at a mean of 8 +/- 4 days after acute MI. Myocardial viability in the infarct zone was documented in 43 of 59 (73%) patients (group 1), in whom mean asynergy score index decreased from 1.6 +/- 0.3 at baseline to 1.3 +/- 0.2 (p < 0.001), after low-dose dobutamine. No viability was present in 16 of 59 (27%) patients (group 2). At follow-up, recovery of regional contractile function was observed in group 1 (asynergy score index decreased from 1.6 +/- 0.3 to 1.4 +/- 0.3; p < 0.001), but not in group 2 patients. Sensitivity, specificity, and negative and positive predictive values of low-dose dobutamine echocardiography in predicting spontaneous recovery of function were 79%, 68%, 50%, and 89%, respectively. Of the 51 patients who underwent high-dose dobutamine, 26 of 36 (72%) group 1 patients showed a deterioration of contractility in the infarct zone indicative of myocardial ischemia compared with only 1 of 15 (7%) group 2 patients. At follow-up, recovery of regional function was greater in patients with no evidence of myocardial ischemia at high doses than in those with an ischemic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Mental arithmetic stress testing in patients with coronary artery disease

A mental arithmetic stress test was performed by 122 consecutive patients undergoing diagnostic coronary arteriography. Twenty-two patients showed significant ST segment abnormalities during the test (group 1). Of these patients, 20 performed a bicycle exercise test, which was positive in all of them. Seventy patients had a negative mental stress but a positive exercise test (group 2), whereas in 30 patients both tests were negative (group 3). There were no patients with a positive mental stress test and a negative exercise test. Mental stress induced a significant increase in heart rate and systolic blood pressure in the three groups of patients. Group 1 patients, however, achieved higher values of double product during mental stress and had a shorter exercise duration than group 2 and group 3 patients. The extent of coronary artery disease (CAD) was similar in groups 1 and 2, while group 3 patients had a significantly lower prevalence of two or more vessel disease. To investigate the pathogenetic mechanism of mental stress-induced myocardial ischemia, great cardiac vein flow was measured by means of the thermodilution technique in four patients with isolated left anterior descending artery disease, who showed ST segment depression in anterior leads in response to mental stress. In three patients without vasospastic angina the calculated coronary resistance decreased during mental stress, as a result of a normal vasodilatory response to the increased myocardial oxygen consumption induced by the test. By contrast, in one patient with variant angina, coronary resistance increased suggesting coronary vasoconstriction. Our findings demonstrate that mental arithmetic stress testing may induce significant ST segment abnormalities in patients with CAD.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma levels of interleukin 2, 6, 10 and phenotypic characterization of circulating T lymphocytes in ischemic heart disease

The purpose of this study was to assess lymphocyte receptors expression in patients with ischemic heart diseases, as well as to measure the plasma levels of interleukin (IL) 2, 6 and 10. T Lymphocytes are found in large numbers in human atherosclerotic plaques, indicating that immune and inflammatory mechanisms are important factors in the pathogenesis of atherosclerosis. Recent data have also implicated T lymphocytes in the pathogenetic mechanism of unstable angina and ischemic heart disease. Three groups of patients were studied: 42 with an acute ischemic syndrome (AIS), 36 with stable angina (SA) and 39 healthy controls. To characterize lymphocyte phenotype, flow cytometry was performed in whole-blood samples. IL-2, IL-6 and IL-10 were measured using the ELISA method. Double fluorescence evaluation showed an increase in CD8+/CD11b+ cells (cytotoxic T lymphocytes) and in CD11b+/CD16+CD56+ cells (NK lymphocytes) in the AIS group and in SA group as compared to the control group (P < 0.05 and P < 0.001, respectively). IL-2 was increased in the AIS and SA groups compared to the control group (AIS 4.5 +/- 0.5 pg/ml; SA 6.3 +/- 0.6 pg/ml; controls 2.4 +/- 0.8 pg/ml, P < 0.05), whereas IL-6 was higher in the AIS group than in the other two groups (AIS 10.8 +/- 1.8 pg/ml; SA 1.8 +/- 0.8 pg/ml; controls 1.2 +/- 0.6 pg/ml, P < 0.0001). These data show that patients with ischemic heart disease have an increase in circulating cytotoxic T lymphocytes and in IL-2 plasma levels, irrespective of their clinical presentation, compared to normal control subjects, whereas IL-6 is elevated only in patients with AIS.

Hemodynamics of volume loading compared with dobutamine in severe right ventricular infarction

To compare the hemodynamic effect of volume loading with that of dobutamine infusion in severe ischemic right ventricular (RV) dysfunction, 11 patients with inferior and RV infarction complicated by low cardiac output syndrome and important hemodynamic derangement (systolic blood pressure < 100 mm Hg, cardiac index < 2.0 liters/min/m2, right atrial pressure > 10 mm Hg) were prospectively studied within 48 hours of symptom onset. After right heart catheterization, volume loading (mean 400 ml saline solution) and dobutamine infusion (5 and 10 micrograms/kg/min over 10 minutes) were performed according to a randomized, crossover design. Volume loading resulted in increased right atrial (from 15 +/- 2 to 19 +/- 3 mm Hg, p < 0.05) and pulmonary capillary (from 15 +/- 2 to 19 +/- 3 mm Hg, p < 0.05) pressures, without increasing cardiac index, heart rate, aortic pressure, or right and left ventricular stroke work index. Dobutamine (5 micrograms/kg/min) increased cardiac index (from 1.5 +/- 0.3 to 1.9 +/- 0.5 liters/min/m2, p < 0.05), incrementing both heart rate (from 61 +/- 12 to 70 +/- 13 beats/min, p < 0.05) and stroke volume index (from 25 +/- 6 to 27 +/- 5 ml/beat/m2, p < 0.05), as well as right (from 1.4 +/- 1.6 to 2.3 +/- 2.2 g.m/m2, p < 0.05) and left (from 21 +/- 7 to 27 +/- 10 g.m/m2, p < 0.05) stroke work indexes; right and left ventricular filling pressures did not decrease. Dobutamine (10 micrograms/kg/min) significantly improved myocardial performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of nifedipine on coronary hemodynamic findings during exercise in patients with stable exertional angina.

To investigate the mechanism by which nifedipine improves exercise tolerance in patients with coronary artery disease, we studied 14 patients with stable exertional angina and left anterior descending artery disease by measuring great cardiac vein flow (GCVF) and calculating anterior regional coronary resistance (ARCR) during exercise before and after sublingual administration of 20 mg of nifedipine. After nifedipine seven patients (group I) had no increase in exercise capacity and showed a similar magnitude of ST segment depression at peak exercise, while another seven patients (group II) had prolonged exercise duration (p less than .001) with less ST segment depression at peak exercise (p less than .01). Such effects were achieved despite a significant increase in double product, an indirect index of myocardial oxygen consumption. In group I patients no significant change was induced by nifedipine in GCVF or in ARCR either at rest or at peak exercise. In contrast, in group II patients nifedipine significantly increased GCVF at rest (p less than .05) and at peak exercise (p less than .001). Moreover, resting ARCR was decreased (p less than .01) and remained significantly lower at peak exercise (p less than .01) compared with the prenifedipine values. These data show that nifedipine may increase GCVF and decrease ARCR at rest and at peak exercise in patients with left anterior descending artery disease. Such increase in myocardial oxygen supply seems the most likely mechanism by which nifedipine may improve exercise capacity in patients with stable exertional angina.

The exercise test in variant angina: results in 114 patients.

One hundred fourteen patients with variant angina performed bicycle exercise stress tests, and were divided into three groups. Group 1 included 37 patients with a normal exercise test. Coronary arteriography revealed absence of significant coronary stenoses in 18 patients, one‐vessel disease in 17 and involvement of two or more vessels in two. Group 2 consisted of 40 patients who had ST‐segment elevation during or just after exercise. Coronary arteriography in these cases revealed absence of significant coronary stenoses in nine patients, one‐vessel disease in 18 and disease of two or more vessels in 13. Group 3 included 37 patients who had ST‐segment depression during exercise. Absence of coronary artery disease was found in only two patients, one‐vessel disease was found in 19 and disease of two or more vessels was found in 16. Sixty‐one patients repeated the exercise test after a mean of 18 months after hospital discharge. Exerciseinduced ST‐segment elevation was no longer present in surgically or medically treated patients; ST‐segment depression was still evident in all the medically treated patients, but was absent in eight of 13 patients who underwent aortocoronary bypass surgery. Exercise testing can be useful in the follow‐up of patients with variant angina and in selecting patients most likely to be helped by bypass surgery.

Significance of exercise-induced ST-segment elevation in patients without myocardial infarction.

SUMMARY Sixteen patients with exercise-induced ST-segment elevation and without a history of myocardial infarction or left ventricular aneurysm were studied. Fourteen complained of angina at rest, which was associated with ST-segment elevation in the same leads where it was recorded during exercise, and two patients had only exertional angina. Exercise-induced ST-segment elevation was generally reproducible in subsequent exercise tests performed in different hours of the day, but exercise tests repeated a mean of 15 months later did not induce this electrocardiographic abnormality. All patients had a marked susceptibility to coronary spasm, as shown by the response to the ergonovine test (12 positive tests in 12 patients) and by the occurrence of spontaneous spasm during coronary arteriography in two patients. In addition, coronary arteriography, performed in seven patients at the time of exercise-induced ST-segment elevation, revealed spasm of a major coronary vessel in all. In two patients we documented that exercise-induced ST-segment elevation was accompanied by a decreased coronary blood flow and increased coronary vascular resistance. We conclude that exercise-induced ST-segment elevation in patients without a history of myocardial infarction or left ventricular aneurysm is caused by coronary spasm of a major coronary vessel.