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.

Antithrombotic therapy of unstable angina and non-Q-wave myocardial infarction.

Unstable angina and non-Q-wave myocardial infarction still represent an unsolved problem for clinicians, owing to their unpredictable evolution and high incidence of coronary events in the follow-up. Traditional antithrombotic agents, unfractionated heparin and aspirin, have been proved to be highly effective, but show some important limitations. New potent antithrombotic therapy have been studied to improve their efficacy, with encouraging results. Among these drugs, low molecular weight heparins (for subcutaneous administration) and inhibitors of platelet glycoprotein receptor IIb/IIIa (for intravenous, and possibly oral, administration) are the most promising and are now under extensive investigation.

Effect of transdermal nitroglycerin or N-acetylcysteine, or both, in the long-term treatment of unstable angina pectoris.

OBJECTIVES: This study was designed to evaluate whether the addition of transdermal nitroglycerin or oral N-acetylcysteine, or both, to conventional medical therapy improves the natural history of unstable angina pectoris. BACKGROUND: Transdermal nitroglycerin is widely used to treat angina pectoris, but the development of tolerance is a major problem that may reduce its clinical efficacy. It has been suggested that the addition of N-acetylcysteine to nitroglycerin reverses the development of tolerance, potentiates the hemodynamic response to nitroglycerin and may improve in-hospital prognosis in unstable angina. METHODS: We assessed the efficacy of adding transdermal nitroglycerin or oral N-acetylcysteine, or both, to conventional medical therapy in a randomized, double-blind, placebo-controlled trial involving 200 patients with unstable angina who were followed up for 4 months. RESULTS: Outcome events--death, myocardial infarction or refractory angina requiring revascularization--occurred in 31% of patients receiving nitroglycerin, 42% of those receiving N-acetylcysteine, 13% of those receiving nitroglycerin plus N-acetylcysteine and 39% of those receiving placebo (p = 0.0052). Kaplan-Meier curves showed a higher probability (p < 0.01) of no failure of medical treatment in the group receiving both nitroglycerin and N-acetylcysteine than in those receiving placebo, N-acetylcysteine or nitroglycerin alone. The combination of nitroglycerin and N-acetylcysteine was associated with a high incidence of side effects (35%), mainly intolerable headache, which was almost twice as frequent as in patients receiving nitroglycerin alone. CONCLUSIONS: The combination of nitroglycerin and N-acetylcysteine, associated with conventional medical therapy in the long-term treatment of patients with unstable angina, reduces the occurrence of outcome events. However, the high incidence of side effects limits the clinical applicability of this therapeutic strategy at least at the dosage used in the present study.

Comparison of dobutamine stress echocardiography with dipyridamole stress echocardiography for detection of viable myocardium after myocardial infarction treated with thrombolysis.

OBJECTIVE: To compare the ability of dobutamine and dipyridamole stress echocardiography to detect functional recovery of stunned but viable myocardial regions early after acute myocardial infarction, and to predict late functional recovery of the reperfusion salvaged myocardium within the infarct area. METHODS: Within 10 d of acute myocardial infarction, 51 patients--30 anterior and 21 inferior, 44 Q wave and seven non-Q-wave infarction--were submitted to a dobutamine echocardiography test at low dose (5-10 micrograms/kg/min over 5 min) and high dose (20-40 micrograms/kg/min over 3 min) and to dipyridamole echocardiography test (0.56 mg/kg over 4 min + 0.28 mg/kg over 2 min) on different days and in random order, after interruption of any vasoactive drug. Resting echocardiography was repeated at two months in 41 of 51 patients (80%). Regional wall motion of the left ventricle was analysed in a semiquantitative manner on a 14-segment model. Viability was defined as improvement of one grade or more of at least two basally asynergic segments in the infarcted area. RESULTS: Regional functional recovery was detected by low dose dobutamine in 38/51 patients (75%) and in 147/308 (48%) of basally asynergic segments, compared to 25/51 patients (49%; P < 0.001) and 78/308 segments (25%; P < 0.001) only identified by dipyridamole. Late spontaneous functional recovery was detected in 24/41 patients (59%) and in 78/254 basally asynergic segments (31%). The sensitivity of dobutamine and dipyridamole echocardiography for predicting spontaneous functional recovery was 72% and 51% respectively (P < 0.001), specificity 68% and 82% (P < 0.001), positive predictive value 50% and 56%, and negative predictive value 85% and 79%. CONCLUSIONS: In comparison with dipyridamole in patients with thrombolysed myocardial infarction, dobutamine induces regional functional recovery. This suggests that dobutamine is more sensitive in showing the presence of viable myocardium within the infarct zone, though it has a lower specificity in predicting delayed spontaneous functional recovery of non-contractile but still viable areas.

[Adding atropine improves the diagnostic accuracy of dipyridamole-echo test]. / L'aggiunta di atropina migliora l'accuratezza diagnostica del test eco-dipiridamolo.

BACKGROUND: The clinical experience with dipyridamole stress echocardiography for the diagnosis of coronary artery disease (CAD) revealed that patients with less severe extent of CAD and limited impairment of coronary reserve are frequently not recognized by the test. Increasing myocardial oxygen consumption adding atropine to dipyridamole may improve the diagnostic accuracy of dipyridamole for the detection of CAD. METHODS: Fifty-two patients (48 men, aged 53 +/- 7 years) underwent a high-dose dipyridamole-echo stress test (0.84 mg/kg over 10 minutes) and coronary arteriography within 15 days from the test. Eighteen out of 52 patients were referred for chest pain; 11 suffered from a previous myocardial infarction (MI) and 23 were studied in the early phase after a first acute MI. Starting after 4 minutes from the end of dipyridamole infusion, atropine was added, in 2 doses of 0.5 mg each, at 1-minute interval in those patients with no echocardiographic evidence of myocardial ischemia after dipyridamole alone. Left ventricular wall motion was analyzed on a 11-segment left ventricular model in a qualitative manner. RESULTS: Dipyridamole-echo stress test was positive in 23/52 (44%) and negative in 29/52 (56%) patients. In these patients atropine was added resulting in an additional echo positivity in 14/29 patients. Coronary arteriography was normal in 6 patients (12%); 1-vessel CAD was diagnosed in 23 (44%), 2-vessel CAD in 13 (25%) and 3-vessel CAD in 10 (19%) cases. The sensitivity for CAD diagnosis was 48% (22/46) for dipyridamole alone and 76% (35/46) for dipyridamole-atropine echo (p < .005), while the specificity was 83% (5/6) and 80% (4/5) respectively. Diagnostic accuracy increased from 52% (27/52) to 75% (39/52) (p < .001). The better diagnostic accuracy of dipyridamole-atropine echo stress test was mainly related to the increased sensitivity of the combined test in patients with 1-vessel CAD (from 39% to 70%) (p < .005). Peak heart rate was significantly higher after the addition of atropine (100 +/- 17 beats/min) compared to basal (64 +/- 10) and dipyridamole (85 +/- 12) in those patients with a positive dipyridamole-atropine echo stress test. No limiting side effects were elicited with the addition of atropine to dipyridamole. CONCLUSIONS: The combination of atropine and dipyridamole induces a chronotropic stress adjunctive to flow maldistribution phenomena that permits to increase diagnostic accuracy of dipyridamole-echo stress test particularly in patients with less severe extent of CAD; it is usually well tolerated and safe and may be considered as a useful procedure for optimizing diagnostic value of dipyridamole-echo stress test.

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)

Haemodynamic effects of glyceryl trinitrate during continuous 24 hour infusion in patients with heart failure.

OBJECTIVE: To investigate whether the susceptibility to tolerance to glyceryl trinitrate is similar in different vascular beds in patients with chronic heart failure. PATIENTS: Twenty patients with heart failure underwent a continuous infusion of glyceryl trinitrate over 24 hours followed by administration of N-acetylcysteine (5 g intravenously) in a bolus. MAIN OUTCOME MEASURES: Haemodynamic measurements under control conditions, at peak titration of glyceryl trinitrate at 24 hours, and after N-acetylcysteine; plasma renin activity and packed cell volume. RESULTS: After 24 hours of infusion the acute reduction in right atrial pressure had largely waned, while pulmonary vascular resistance remained improved and systemic resistance, which was not reduced at peak titration, significantly decreased with respect to control conditions. The effects of N-acetylcysteine and hormonal responses were different in patients who did and did not develop tolerance to glyceryl trinitrate. CONCLUSIONS: The haemodynamic profile of glyceryl trinitrate changed substantially during the study from a predominantly venodilator action at peak titration to a predominantly arteriolar dilatation after 24 hours of infusion. The different effects of N-acetylcysteine and the different hormonal responses confirm the multifactorial pathogenesis of tolerance to glyceryl trinitrate.

[Echocardiography-dobutamine test in the short-term evaluation of the results of coronary angioplasty]. / Il test eco-dobutamina nella valutazione a breve termine dei risultati dell'angioplastica coronarica.

BACKGROUND: Coronary angioplasty is commonly performed as a means of coronary revascularization, but at present no method has proven to be of definite value in assessing the functional result of a given angiographic procedure. OBJECTIVES: The purpose of this study was to evaluate whether dobutamine stress echocardiography can detect a reversal of ischemia-induced left ventricular regional wall motion abnormalities 15 days after an angiographically successful percutaneous transluminal coronary angioplasty (PTCA). METHODS: 25 patients underwent dobutamine stress echocardiography 24-48 hours before and 15 days after an elective angiographically successful PTCA. Twelve out of 25 patients (48%) suffered from a previous myocardial infarction. Symptomatic myocardial ischemia was documented before PTCA in 18/25 patients (72%) and asymptomatic ischemia in 7/25 (28%). Dobutamine was infused utilizing incremental steps of 5 mcg/kg/min over 3 minutes, up to a maximal dose of 40 mcg/kg/min. Echocardiographic images were stored on video tape and analyzed in a qualitative manner by two independent and experienced cardiologists without knowledge of the angiographic data. An asynergy score (from 0 = normal to 3 = dyskinesia) was calculated using a 14-segment left ventricular model in basal conditions and at peak stress, before and after PTCA. All tests were performed taking the patients off the antianginal therapy. RESULTS: One-vessel coronary artery disease was present in 18/25 (72%) patients, and two-vessel disease in 7/25 (28%) four of these 7 patients underwent PTCA on both involved vessels; mean diameter of the stenosis was 91 +/- 6% before PTCA, and was reduced to 22 +/- 8% after PTCA. Dobutamine stress echocardiography induced wall motion abnormalities in 24/25 patients before and in 4/25 after PTCA; the frequency of dobutamine-induced wall motion abnormalities significantly decreased from 96% to 12% before and after angioplasty (p < .01). All patients developed regional wall motion abnormalities in the region supplied by the dilated vessel. Wall motion score at peak dobutamine infusion improved from 8.5 +/- 4.8 before PTCA to 2.6 +/- 4.9 after PTCA (p < .001). There was a significant increase in the rate-pressure product achieved during the test after PTCA (21300 +/- 400 bts/min.mmHg) compared to the test performed before PTCA (19000 +/- 500 bts/min.mmHg) (p < .05). Dobutamine induced angina in 6/25 patients (24%) and ST-segment changes in 19/25 patients (76%) before PTCA, whereas angina occurred only once after PTCA and ST-segment changes 6 times only after PTCA. No major side effects occurred during dobutamine infusion both before and after PTCA. CONCLUSIONS: Our study indicates that dobutamine stress echocardiography is a feasible and safe method that accurately demonstrates an early improvement in stress-induced regional left ventricular dysfunction after an angiographically successful coronary angioplasty.

[The echo-dobutamine and echo-dipyridamole tests in assessing vital myocardium and residual ischemia in myocardial infarct after thrombolysis]. / Il test eco-dobutamina ed eco-dipiridamolo nella valutazione del miocardio vitale e dell'ischemia residua nell'infarto miocardico dopo trombolisi.

The aim of the study was to compare the ability of dobutamine and dipyridamole echocardiography to detect stunned but viable myocardium early after acute myocardial infarction, to predict spontaneous functional recovery of the reperfused myocardium at 2 months and to detect myocardial ischemia in the infarcted area. Within 10 days from acute myocardial infarction, 47 patients, 29 anterior and 18 inferior, 41 Q-wave and 6 non Q-wave infarctions, underwent dobutamine echocardiography test at low-dose (5-10 mcg/kg/min over 5 min) and high-dose (20-40 mgc/kg/min over 3 min) and to dipyridamole echocardiography test (0.56 mg/kg over 4 min + 0.28 mg/kg over 2 min) in different days and in random order, after interruption of any vasoactive drug. Resting echocardiography was repeated at 2 months in 38/47 patients. Regional wall motion analysis was performed in a qualitative manner on a 14-segment model; viability was defined as improvement of 1 grade or more of at least 2 basally asynergic segments in the infarcted area. Ischemia was defined as an improvement followed by significant deterioration of contractility of the infarcted segments or deterioration of the infarcted area. All patients underwent coronary arteriography within 1 month from admission. Viability was detected by low-dose dobutamine in 34/47 patients (72%) and in 131/297 (44%) of basally asynergic segments compared to only 21/47 patients (45%) and in 66/297 segments (22%) detected by dipyridamole; myocardial ischemia was induced by dobutamine in 64% of patients compared to 36% by dipyridamole. Late spontaneous functional recovery was detected in 21/38 patients (57%) and in 70/244 (29%) of asynergic segments. Sensitivity of dobutamine and dipyridamole echocardiography for predicting spontaneous functional recovery was 70% and 46% specificity 69% and 83%, positive predictive value 48% and 52%, negative predictive value 85% and 79% respectively. Dobutamine correctly identified the presence of a significant stenosis of the infarct-related artery in 74% of cases compared with 43% of dipyridamole; specificity for detecting stenosis was 67% for dobutamine and 83% for dipyridamole. In conclusion, in patients with thrombolyzed myocardial infarction dobutamine echocardiography detects viable myocardium with late spontaneous recovery in a greater proportion of patients and segments than dipyridamole; dobutamine has a higher sensitivity but a lower specificity compared to dipyridamole for identifying a residual stenosis of the infarct-related artery that may jeopardize myocardium in the area at risk.

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)

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.

[Hemodynamic effects of enalapril in patients with non-complicated acute myocardial infarct]. / Effetti emodinamici dell'enalapril in pazienti con infarto miocardico acuto non complicato.

To evaluate the hemodynamic effects of the first oral administration of enalapril maleate, a long-acting ACE-inhibitor, in the early phase of an acute uncomplicated myocardial infarction, we studied 15 patients, in Killip class I or II, within 72 hours from the onset of symptoms. Hemodynamic measurements were obtained by a triple lumen 7 F Swan-Ganz catheter, inserted into the pulmonary artery, under control conditions and 2, 4, 6, 8 and 12 hours after 10 mg (15 patients) and 20 mg (11 patients) of the drug. Ten milligrams of enalapril reduced systolic and mean arterial blood pressure (from 118 +/- 17 to 111 +/- 18 mmHg, p < .05, and from 92 +/- 12 to 83 +/- 12 mmHg, p < .01, respectively), with a maximum effect after 4 hours from administration. Heart rate and vascular resistances showed an insignificant trend toward reduction, and no changes were observed in left ventricular systolic work index, right and left ventricular filling pressures or cardiac index. Hemodynamic changes induced by 20 mg of the drug, in a smaller group of patients, had a similar trend, which did not reach a statistical significance. In conclusion, in patients with acute uncomplicated myocardial infarction, a single oral dose of enalapril maleate is safe and well tolerated, does not induce severe hypotension, and produces potentially beneficial changes in hemodynamics.

[Comparison of results of echo-dobutamine and ECG-dobutamine tests in the diagnosis of coronary disease]. / Confronto fra i risultati dei test eco-dobutamina ed ecg-dobutamina per la diagnosi di malattia coronarica.

The aim of the study was to compare the results of 2D-Echocardiographic (ECHO) vs 12-lead Electrocardiographic (ECG) monitoring during Dobutamine (DOB) infusion performed as a stress test in patients referred for the evaluation of chest pain of suspected ischemic origin. Fourty-seven consecutive patients, 40 m and 7 f, mean age 52 +/- 9 years, were studied after interruption of any antianginal therapy. DOB was infused in 5-minute stages with incremental doses of 5 mcg/kg/min up to a maximal dose of 40 mcg/kg/min. 2D-ECHO monitoring could not be performed in 3 out of 47 patients because of a poor acoustic window. Thus, the overall feasibility was 94% for 2D-ECHO DOB test vs 100% for ECG DOB test (p = ns). The ECG and 2D-ECHO findings were compared in the remaining 44 patients. Criteria for positivity were: transient regional dyssynergy absent or of lesser degree in the baseline examination for 2D-ECHO; ST-segment shift > 0.1 mV from baseline for ECG. The test was stopped when a regional wall motion abnormality developed even in the absence of significant ECG changes. Angiographically assessed coronary artery disease (CAD) was considered significant when a > 50% reduction of the luminal diameter in at least 1 major coronary vessel occurred. There were 10/44 patients with no significant CAD and 34/44 patients with CAD; 16 had single, 18 double or triple and/or left main vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Dobutamine-induced ST segment elevation in a patient with angina at rest and critical coronary lesions.

A case of dobutamine-induced ST-segment elevation in a patient with angina at rest and severe two-vessel disease is described. Coronary angiography performed during the ischaemic episode showed patency of coronary arteries; ST-segment elevation and chest pain regressed after propranolol administration. This case suggests that in the presence of severe coronary lesions dobutamine may produce transmural myocardial ischaemia by increasing myocardial oxygen demand and inducing myocardial blood flow maldistribution.

Felodipine (once daily) versus nifedipine (four times daily) for Prinzmetal's angina pectoris.

In 30 consecutive patients with Prinzmetal's angina pectoris, the antiischemic effect of felodipine, a new long-acting vasoselective calcium antagonist, administered at doses of 10 and 20 mg once daily was compared with that of the well-established therapeutic regimen with nifedipine administered at a dose of 20 mg 4 times daily. Twenty-four-hour Holter monitoring was performed during a 2-day placebo run-in and at the end of each of 3 consecutive 6-day periods during which the 3 active treatments were administered in randomized sequence. Three patients withdrew, whereas 27 completed the study. The therapeutic regimens tested proved to be similarly effective; primary end points (ischemic episodes recorded by Holter monitoring, and anginal attacks reported on diary cards) occurred in 5 patients (19%) during nifedipine treatment, and in 7 (26%) and 3 (11%) during felodipine treatment with 10 and 20 mg, respectively (p = not significant). The distribution of residual ischemic episodes demonstrated that treatment with felodipine once daily provides 24-hour antiischemic protection. Twenty-six patients were followed up with 20 mg of felodipine once daily for a mean of 6 +/- 5 months, and 21 of them (81%) remained free of symptoms and Holter-recorded ischemic attacks. It is concluded that for Prinzmetal's angina pectoris, 24-hour antiischemic protection may be achieved with administration of felodipine once daily. The availability of a simplified therapeutic approach may constitute a real advantage in terms of patient compliance and improving the quality of life.

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.

Dobutamine versus dipyridamole echocardiography in coronary artery disease.

Dobutamine and dipyridamole echocardiography are gaining popularity as exercise-independent stress tests for the diagnosis of coronary artery disease. To compare the feasibility, sensitivity, and specificity of dobutamine echocardiography to dipyridamole echocardiography, we conducted both tests, on different days and in random order, on 35 patients with chest pain and suspected coronary artery disease. Dobutamine was administered in scalar doses up to 40 micrograms/kg per minute and dipyridamole up to 0.84 mg/kg for 10 minutes. Dobutamine echocardiography testing was positive in eight of 16 (50%) patients with single-vessel disease and in 11 of 12 (92%) patients with multivessel disease, resulting in an overall sensitivity of 68% for the presence of coronary artery disease. Dipyridamole echocardiography testing showed the same sensitivity as dobutamine in patients with multivessel disease but a lower sensitivity (31%) in single-vessel disease, resulting in an overall sensitivity of 57%. The specificity of both tests was 100%. An ST segment shift of more than 1 mm compared with baseline was documented in 74% of the positive dobutamine echocardiography tests and in 81% of the positive dipyridamole echocardiography tests. No major complications occurred during both tests. Ventricular arrhythmias occurred in 11 patients with dobutamine and in none with dipyridamole (31% versus 0%, p less than 0.001). Thus, in our selected population dobutamine echocardiography testing demonstrated a similar overall sensitivity and specificity for the diagnosis of coronary artery disease compared with dipyridamole, with a slightly better sensitivity for single-vessel disease but a greater arrhythmogenic potential.

[Expansion of the infarct area in anterior myocardial infarct: a short-term clinical and echocardiographic study]. / L'espansione dell'area infartuale nell'infarto miocardico anteriore: studio clinico ed ecocardiografico a breve termine.

Forty-five patients with a first anterior myocardial infarction were studied by serial two-dimensional echocardiographic examinations to evaluate the incidence, short-term evolution and clinical significance of infarct expansion. Infarct expansion was found in 26 patients (58%); in 22 cases it was detected at the first examination 24 hours after the onset of symptoms, while in the other 4 it developed later. In 20 (77%) patients expansion involved only the septal and apical regions, while in 6 (23%) it extended to the antero-lateral wall. Two out of 22 patients with early expansion died of cardiogenic shock; expansion of the infarcted area progressively increased in 10 of the remaining 20 patients and remained stable in the other 10. Compared to the patients without expansion those with expansion had a higher CK peak level, a greater number of pathological Q waves and a greater echocardiographic asynergy score; moreover, in-hospital mortality and the incidence of left ventricular failure were higher in the group with expansion (8% vs 0% and 54% vs 10% respectively). Thus our results show that in patients with anterior infarction, expansion is a frequent event which usually develops early and may have a progressive course; infarct expansion, especially when it is large and progressive, is associated with a high incidence of early left ventricular failure and has a poor prognostic significance.

[Comparison of two-dimensional echocardiography and hemodynamic monitoring in acute myocardial infarct]. / Confronto fra ecocardiografia bidimensionale e monitoraggio emodinamico nell'infarto miocardico acuto.

The aim of this study was to assess if in patients with acute myocardial infarction, two-dimensional echocardiographic asynergy index is correlated to hemodynamic parameters. Furthermore, we compared how reliable the 2 methods are to identify patients at a high risk of developing early left ventricular failure. Fifty-four consecutive patients (43 males, 11 females, mean age: 61 +/- 13 years with acute myocardial infarction were studied using hemodynamic monitoring and 2D-echocardiography within 24 hours from admission. The 2D-echo asynergy index, calculated on a 14-segment left ventricular model, was significantly correlated to heart rate (r = 0.49, p less than 0.001), pulmonary capillary wedge pressure (r = 0.47, p less than 0.001), systemic vascular resistance (r = 0.47, p less than 0.001), cardiac index (r = -0.46, p less than 0.001) and left ventricular stroke work index (r = -0.63, p less than 0.001). Both the asynergy index and the hemodynamic parameters were correlated to Killip clinical classification. In the sub-group of 46 patients initially classified as belonging to Killip class I or II, the patients who later developed left ventricular failure or those in whom it worsened showed a higher asynergy index and a greater impairment of left ventricular function when compared to the patients with an uncomplicated clinical course. The sensitivity of an asynergy index greater than or equal to 1 in predicting early cardiac failure was 75%, the specificity was 64%, the positive predictive value was 43% and the negative predictive value was 88%.(ABSTRACT TRUNCATED AT 250 WORDS)

Recombinant tissue-type plasminogen activator followed by heparin compared with heparin alone for refractory unstable angina pectoris.

Patients with unstable angina pectoris who remain symptomatic despite medical treatment are at high risk of death and myocardial infarction. The incidence of refractory unstable angina was examined in a consecutive series of 103 patients who received conventional medical treatment with nitrates, beta blockers, calcium antagonists and aspirin. During 48 hours of continuous electrocardiographic monitoring, 24 patients had greater than or equal to 1 anginal attack, 5 of whom had both painful and painless ischemic episodes. In these 24 patients with unstable angina refractory to conventional medical treatment, the short-term efficacy of recombinant tissue-type plasminogen activator (rt-PA) followed by heparin was assessed and compared with heparin alone in a randomized double-blind trial. Recurrences of ischemic attacks during a 72-hour follow-up period were documented in 9 of the 12 patients given heparin alone. All patients experienced at least 1 symptomatic ischemic episode and 1 patient had both painful and painless ischemia. No patient given rt-PA plus heparin had either symptomatic or asymptomatic ischemic attacks during follow-up. Kaplan-Meier curves analysis demonstrated a significantly higher probability of being ischemia free in the group of patients treated with rt-PA followed by heparin than in the group treated with heparin alone (p less than 0.01). Quantitative coronary arteriography failed to reveal any significant changes of ischemia-related lesions before and after each treatment. This study demonstrates that the combination of rt-PA and heparin has a greater protective effect than heparin alone in treating recurrent ischemic episodes in patients with refractory unstable angina.(ABSTRACT TRUNCATED AT 250 WORDS)