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Background: The blood coagulation system is frequently activated in the acute phase of unstable angina, but it is unknown whether the augmented function of the hemostatic mechanism may serve as a marker of increased risk for an early unfavorable outcome., Methods and Results: Plasma concentrations and 24-hour urinary excretion of fibrinopeptide A were prospectively determined in 150 patients with unstable angina. All patients underwent 24-hour Holter monitoring, during which time urine was collected; at the end of this period, a blood sample was taken and coronary arteriography was performed. The patients were followed up for the occurrence of cardiac events (death and myocardial infarction) until they underwent coronary revascularization or until they were discharged from the hospital. Fibrinopeptide A plasma levels and 24-hour urinary excretion were found to be abnormally elevated in 50% and 45% of the study population, respectively. During hospitalization, 11 patients developed myocardial infarction and 2 patients died. Kaplan-Meier analysis demonstrated a significantly higher probability of developing cardiac events in patients with abnormal rather than normal plasma levels of fibrinopeptide A (P<.01), whereas no difference in outcome was observed between patients with normal and those with abnormal 24-hour urinary excretion. Cox regression analysis showed that the only variables independently related to an early unfavorable outcome were the presence of persistent ischemia during 24-hour Holter monitoring (P<.0001), the presence of intracoronary thrombosis at angiography (P=.016), and abnormal fibrinopeptide A plasma levels (P=.038)., Conclusions: Patients with unstable angina pectoris and abnormal fibrinopeptide A plasma levels are at increased risk for an early unfavorable outcome.

Background: Patients with non-Q wave myocardial infarction (NQ AMI) are usually considered to have an increased risk of recurrent ischemic events and reinfarction. We wished to assess whether dobutamine stress echocardiography with the addition of atropine (DOB-E + ATRO) can detect jeopardized myocardium after a recent NQ AMI and to assess the prognostic significance of this test in a group of patients with a first uncomplicated NQ AMI:, Methods and Results: Fourty-one consecutive patients (38 men, mean age 52 +/- 9 years, 31 anterior, 68% treated with thrombolysis) underwent low and high-dose DOB-E (from 5 to 40 mcg/kg/min); ATRO was added in 14/41 (34%) patients. A significant deterioration of wall motion in the infarcted region (IR) indicative of residual myocardial ischemia was present in 36/41 patients (88%). Significant electrocardiographic changes and angina developed in 61% and 32% of patients, respectively. Coronary angiography was performed in 30/41 patients (73%) and showed 1-vessel coronary artery disease (CAD) in 70% of cases, multivessel CAD in 23% of cases and no significant CAD in 7% of patients. Three patients were lost at follow-up and 10 other patients were excluded from the analysis because a revascularization procedure was performed during diagnostic angiography. On a mean follow-up period of 9.5 +/- 9 months, the incidence of coronary events (re-infarction, recurrent angina, revascularization procedures) was higher (15/36 vs 1/5, 42% vs 20%) in patients with a DOB-E + ATRO positive test (1 reinfarction, 9 recurrent angina, 5 revascularized) than in those with a negative test (1 recurrent angina)., Conclusions: DOB-E + ATRO early after a first uncomplicated NQ AMI documents the presence of myocardial ischemia in the IR in the great majority of patients. A positive DOB-E + ATRO was found to be associated with a higher incidence of cardiac events at follow-up, but the results of this non prospective study (high sensitivity but low specificity and predictive value for cardiac events at follow-up) suggest to utilize with caution this test for risk stratification of patients with recent NQ AMI until prospective and larger studies are performed.

Background: The decreased availability of economic resources, opposed to the increased demand for medical assistance, requires the use of methods to assess hospital efficiency. Purpose of our study was to evaluate and quantify the "products" of a cardiology department, as well as the changes in time of their production, by means of a catalogue of medical acts, set up for the French health system (CdAM)., Methods: The study includes the 224 admissions occurring in October 1987 and the 209 admissions of October 1992. Medical acts were recorded for all admissions, by number of acts as well as by weight of acts; this weight (expressed as complexity/cost index or ICR) takes into account the use of resources in terms of medical staff and nursing staff, together with technical resources, for each act. In 1987 and 1992, 1736 and 1603 acts were performed respectively, corresponding to a total weight of 24308 and 32194 ICR., Results: The increased ICR appears to be related to an increase of invasive procedures, particularly of interventional electrophysiology and haemodynamics. By considering case mix, we observed an increment of ICR for the diagnosis of angina (from 194.3 to 227.4 ICR per patient), of arrhythmias (from 178.0 to 273.1) and of cardiomyopathy (from 95.6 to 179.7)., Conclusions: In conclusion, CdAM allows to evaluate the cardiologic activity also in the Italian situation; the ICR of each act permits to estimate the human and technical burden, with subsequent easy internal and external comparisons.

Objective: To evaluate the efficacy and safety of simvastatin administered to a group of heart transplant patients receiving triple-drug immunosuppressive therapy. We also assessed the potential pharmacokinetic interaction between simvastatin and cyclosporine by comparing mean plasma concentrations of simvastatin beta-hydroxy acid, the major metabolite of the drug, in a group of heart transplant patients treated with cyclosporine and in a control group of patients who had not received heart transplants. Both groups received long-term (> 6 wk) simvastatin therapy., Design: We monitored hyperlipidemia in 20 hypercholesterolemic heart transplant patients receiving simvastatin 10 mg/d and triple-drug immunosuppressive therapy. Changes in laboratory results before and after 4 months of simvastatin therapy were considered. The same laboratory data were monitored in a control group of 20 nonhypercholesterolemic heart transplant patients who were not treated with simvastatin but were receiving triple-drug immunosuppressive therapy. Plasma concentrations of simvastatin beta-hydroxy acid were measured in 14 hypercholesterolemic patients, 7 of whom had received heart transplants and 7 who had not., Setting: The Division of Cardiology and the First Medical Clinic for the clinical study, as well as the Department of Pharmacology for the pharmacokinetic analysis., Participants: Forty heart transplant patients and 7 hypercholesterolemic nontransplant patients., Main Outcome Measures: Effectiveness of simvastatin was determined by comparing cholesterol and lipoprotein plasma concentrations in 20 patients who underwent heart transplant and were treated with simvastatin for 4 months. The safety of the drug was determined by analyzing changes in laboratory results in the treated group and in the control group, both those who had received heart transplants and those who had received immunosuppressive therapy., Results: After 4 months of simvastatin therapy, total cholesterol decreased by 12.5% and low-density lipoprotein cholesterol decreased by 21.3%. The only statistically significant laboratory change was an increase of 28.7% in the alanine aminotransferase concentrations. Plasma concentrations of simvastatin beta-hydroxy acid were higher in heart transplant patients than in those who had not received heart transplants, the control group., Conclusions: Low-dosage simvastatin treatment seems to be safe and sufficiently effective to decrease cholesterol concentrations. Concomitant treatment with immunosuppressive therapy (primarily cyclosporine) in heart transplant patients appeared to cause a reduced metabolic clearance of simvastatin from the plasma. More extensive studies on the interaction between simvastatin and cyclosporine are needed to understand the marked variability found in the response to simvastatin.

Background: A potential limitation to the clinical utilization of dobutamine stress echocardiography is the higher incidence of side effects in respect to other noninvasive tests for the diagnosis of coronary artery disease reported by some authors. Due to the increased utilization of this test for the evaluation of chest pain and for prognostic stratification in patients with a recent myocardial infarction, we analyzed the results of 373 consecutive tests to evaluate the incidence and clinical significance of side effects induced by dobutamine., Methods: Dobutamine stress echocardiography was performed in 256 patients (69%) for the evaluation of chest pain; 85 out of 256 (33%) suffered from a previous myocardial infarction. 117 patients (31%) were studied in the early phase after an acute myocardial infarction for prognostic purposes. Dobutamine was infused starting with the dose of 5 gamma/kg/min over 3 minutes with incremental steps of 10-20-30-40 gamma/kg/min over 3 minutes under 2D-echocardiographic and 12-lead electrocardiographic monitoring., Results: In 95% of cases the test was stopped at the achievement of a target end point: wall motion abnormalities (60%), significant ECG changes (5%), 85% of the age-predicted maximal heart rate (13%), maximal dose (17%); only in 5% of cases a limiting side effect requiring a premature interruption of the test occurred: hypertension (systolic blood pressure over 240 mm Hg and/or diastolic over 120 mm Hg) (2%); symptomatic hypotension (0.5%); severe chest pain (1%); nausea (0.5%); cardiac arrhythmias (1%). Cardiac arrhythmias were the most frequently registered non limiting side effect. During the test 79 episodes of supraventricular arrhythmias and 211 episodes of ventricular arrhythmias occurred. Supraventricular arrhythmias consisted usually of benign sporadic premature beats; only 3 cases of self-limiting supraventricular tachycardia or atrial fibrillation were recorded. Sporadic ventricular premature beats were the most frequently recorded arrhythmias; 10 patients developed a ventricular tachycardia; however in no case this arrhythmia was sustained, associated with subjective symptoms and required the administration of a specific antiarrhythmic drug or the premature interruption of the test. Patients were divided according to the absence (Group 1, G1, n = 193, 52%) or the presence (Group 2, G2, n = 180, 48%) of cardiac arrhythmias during the test. Patients of G2 differed from patients of G1 only in respect of the maximal dose of dobutamine infused (33.5 vs 28.6 gamma/kg/min, p < 0.0005) and the incidence of a wall motion abnormality in the basal echocardiogram (66% vs 53%, p < .01). The second most recorded non limiting side effect (71/373 pts) (19%) was the occurrence of systolic hypotension, a drop of systolic blood pressure > or = 20 mm Hg in respect of the antecedent infusion step. In all cases no symptoms developed and the great majority of patients with this finding had a normal echocardiographic response to dobutamine at the time of his occurrence., Conclusions: Dobutamine echo stress test is limited by the occurrence of significant side effects only in a minority of patients (5%); however in all cases, including complex ventricular arrhythmias, these side effects were self limiting and promptly recovered after interruption of the drug infusion. Non limiting side effects, in particular cardiac arrhythmias and systolic hypotension, are usually well tolerated and not associated with the occurrence of myocardial ischemia or left ventricular disfunction; thus, dobutamine echo stress test may be considered a safe test for the evaluation of the presence and severity of coronary artery disease both in patients with a previous or recent myocardial infarction and in patients without myocardial infarction.

Background: Aim of this study was to evaluate the factors affecting the duration of the recovery time (RT) after a positive exercise stress test and to define its relationship with the extent of coronary artery disease (CAD)., Methods: We studied 109 consecutive patients with a positive exercise test and proven coronary disease., Results: RT was neither related to the severity of CAD, nor to exercise duration, rate-pressure product at the end of the exercise and maximum ST segment depression. A significant linear relationship was found between RT and the time of ischemia during exercise (IT) (r = 0.66, p < .001). This relationship was analyzed separately in patients (pts) with advanced (Group I) and in pts with less severe CAD (Group II). The regression line of the data showed a similar slope but a higher y-axis intercept in Group I than in Group II (p < .05). The RT/IT ratio was in fact significantly higher in Group I than in Group II (3.0 +/- 1.3 vs 1.7 +/- 0.7, p < .0001). Discriminant analysis was performed to predict the presence of advanced CAD: using the RT/IT ratio instead of RT correct classification rate of the model increased from 81.4 to 86.7%, predictive accuracy from 73.7 to 85.3% and true negative rate from 85.3 to 87.4%., Conclusions: These results suggest that the normalization of the recovery time by time of ischemia during the test provides a simple and useful index for the prediction of the extent of coronary artery disease.

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.

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)

Objective: To compare the efficacy and safety of captopril twice a day with quinapril once a day for the treatment of mild to moderate congestive heart failure in a multicentre, double-blind, randomly allocated, parallel-group, 12-week study., Methods: Exercise capacity, M-mode echocardiographic left ventricular measurements and clinical signs and symptoms were evaluated. After a 2-week, single-blind, placebo washout period, the patients were randomly allocated to double-blind treatment with either captopril twice a day or quinapril once a day; the initial doses of 12.5 and 5 mg, respectively, were increased to 25 and 10 mg, respectively, in the first month, and 50 and 20 mg in the second and third months, as required to achieve adequate blood pressure control. Baseline diuretic and/or digitalis therapy was allowed during the study, so that the patients were maintained in a stable condition., Results: Data from 70 captopril- and 76 quinapril-treated patients were analysed. Both angiotensin converting enzyme inhibitors displayed comparable efficacy. Both drugs were well tolerated, with a low drop-out rate (11.4% for captopril and 10.5% for quinapril)., Conclusion: Treatment with 20 mg quinapril once a day was as effective and safe for the treatment of congestive heart failure as 100 mg captopril administered twice a day.

Background and Methods: We analyzed the complications of 1729 pacemakers implants (from October 1980 to December 1992) divided according to the way of leads insertion. The approaches from the subclavian vein was used in 1220 cases, the cephalic vein was used in 431 implants and the external jugular vein in 78., Results: Major complications were: pocket bleeding (108 cases), pocket erosion (15 cases), infection (2 cases), lead fracture (5 cases), lead dislodgement (20 cases), pneumothorax (4 cases, only for subclavian puncture). There were no significative differences in the complications between the three approaches. On the other hand, the subclavian puncture reduces the time of the procedure, is less traumatic and allows to insert and to position several leads., Conclusions: We suggest to use the subclavian vein approach as first choice to implant one or more leads, being this way safe and fast.

Aim of this study was to analyze the cardiovascular response to graded physical exercise in patients who have undergone cardiac transplantation and to assess the ability of exercise stress testing in early detection of coronary artery disease. We studied 114 transplanted subjects (100 men and 14 women, mean age 46.6 +/- 11.3 years), who performed exercise stress testing 6 months after bypass and then every 6 (+/- 1) months during a 5-year follow-up. Variations of hearth rate (HR), systolic blood pressure (SBP), heart rate-pressure product (RPP) values and exercise stress tolerance were studied both in basal and maximum workload conditions. Mean HR values at basal conditions (103.9 +/- 11.3 b/min at 6 months and 89 +/- 12.7 b/min at 60 months, p < 0.05) and maximum workload tolerance (67.7 +/- 20.4 W at 6 months and 100 +/- 17 W at 60 months, p < 0.05) were significantly different at the beginning and at the end of follow-up. SBP values both at basal conditions and at peak exercise had always been constant. Exercise was stopped for leg muscle fatigue in 92% and dyspnea in 7% of the subjects; isolated T-wave and ST segment changes were found in 29.8% and in 10.5% of the patients respectively, whereas 11.4% exhibited both ST-T variations. Angiographic examination (performed in 80/114 patients) showed significant coronary disease (stenosis > 50%) in 8, coronary atherosclerosis (CAD) of minor degree in 4 and provoked spasm in 2 subjects. In this subgroup exercise stress testing induced ischemic ECG changes (ST segment depression > or = 1 mm) without angina in 1 patient, ST-T segment variations only in 5 and no electrocardiographic alterations (negative tests) in 2 patients. Four subjects with CAD and 1 with coronary spasm induced by angiography showed isolated ST segment and T-wave changes. Our work demonstrated that exercise stress testing plays a relevant role in the study of the denervated heart response to dynamic exercise. The rise in workload tolerated, observed in our population, seems to be related to time elapsed from surgery, improvement in clinical conditions, psychological stability and patient's confidence in his own abilities. The tolerance to exercise 6 months after graft seems to predict the quality of performance in the following tests. Our angiographic results reveal a low sensitivity of the exercise stress test in detecting CAD in this population according to traditional electrocardiographic criteria for myocardial ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)

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 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.

Aim of the study was to assess the relative susceptibility to the development of nitroglycerin tolerance in the arterial and venous circulation in man and to evaluate the interactions between nitroglycerin and N-acetylcysteine. Twenty patients with coronary artery disease underwent a continuous 24-h nitroglycerin infusion followed by a bolus administration of N-acetylcysteine. Forearm blood flow (ml/100 ml/min) and venous volume (ml/100 ml) were measured by strain gauge plethysmography under control conditions, at the end of nitroglycerin titration, after 24 h of infusion and after N-acetylcysteine; vascular resistance was calculated as mean cuff blood pressure/flow. After 24 h of nitroglycerin infusion, the initial increase in venous volume was reduced by 48% (p < 0.01), while the acute effects on vascular resistance were not attenuated in the whole group. N-acetylcysteine restored nitroglycerin venodilator effects in all 10 patients who developed venous tolerance but did not change significantly vascular resistance in 5 patients in whom attenuation of the arterial effects was observed during the infusion period. In conclusion, the results indicate that the susceptibility to the development of nitrate tolerance in man is higher in the venous than in the arterial circulation and that the sulphydryl group donor N-acetylcysteine is more effective in reversing nitroglycerin tolerance in the venous than in the arterial circulation.

Background: Vasoconstriction of normal coronary arteries has been reported after intracoronary (i.c.) administration of acetylcholine (Ach) in cardiac transplant patients and has been related to early endothelial disfunction; the clinical correlates of this response are still unknown., Methods: We infused graded i.c. concentrations of Ach in 32 pts with angiographically smooth coronary arteries 1 to 3 years after heart transplantation. Changes in diameters of the proximal and middle segments of the left anterior descending coronary artery were measured by quantitative coronary angiography (automatic edge detection)., Results: The response to Ach ranged from +44% to -58%; at linear regression analysis it was significantly related to the plasma levels of cyclosporine (r = -0.39, p < .05) and triglycerides (r = -0.42, p < .02) but not to vessel diameter, recipient and donor age, time after transplantation, hypertension, cholesterol levels, number of acute rejection episodes and previous cytomegalovirus infections., Conclusions: In heart transplant pts with angiographically normal coronary arteries i.c. Ach may reveal endothelial disfunction which is associated with high cyclosporine and triglycerides plasma levels. Whether this response may predict an earlier development of coronary disease remains to be elucidated.

The handgrip test has been proposed for the evaluation of the hemodynamic reserve in patients with coronary artery disease and to quantitate the impairment of left ventricular (LV) function. The present study was designed to evaluate the effect of thrombolytic therapy in patients with refractory unstable angina in order to test the hypothesis that a reduction in intracoronary thrombosis could ameliorate their hemodynamic response to the handgrip test. During left heart catheterization, 20 patients with refractory unstable angina of recent onset performed a handgrip test before (HG1) and 24-72 hours after (HG2) being randomized to receive recombinant tissue-type plasminogen activator or placebo, according to a double-blind parallel group design. HG1 induced an increase in heart rate (p < 0.001), in systolic pressure (p < 0.001), and a reduction in ejection fraction (p < 0.05). Changes in LV end-diastolic pressure during baseline handgrip were highly different in individual patients, resulting in a trend toward an increase. Similarly, a different individual response was observed in the behavior of the isovolumetric and relaxation indices. In comparison with HG1, no difference was detected during HG2 in the 2 treatment groups with respect to changes in LV volumes, ejection fraction, LV systolic and diastolic pressures, +dP/dt, (dP/dt)/P, -dP/dt, and tau index. In patients with refractory unstable angina of recent onset, the handgrip test performed before and after thrombolysis did not prove to be useful in assessing directional changes of LV performance, mainly because of the different individual response to the baseline handgrip test.

Objectives: The aims of this study were to correlate beta-endorphin plasma levels and anginal pain in patients with ischemia induced by percutaneous transluminal coronary angioplasty and to detect eventual endorphin variations during balloon occlusion., Background: The opioid system appears involved in the absence of pain occurring in silent myocardial ischemia., Methods: Beta-endorphin plasma levels were measured 24 h before, just before, during and after coronary angioplasty (performed on the left anterior descending artery) in 53 men with documented coronary artery disease and exercise-induced myocardial ischemia., Results: Group 1 (33 patients) reported symptoms; group 2 (20 patients) was asymptomatic during angioplasty. In these patients, the prevalence of exercise-induced silent ischemia was 57%. The occurrence of angina during exercise or angioplasty was related to the frequency of angina during daily life when patients were subgrouped. The severity and distribution of coronary artery disease did not differ between the two groups. During angioplasty, the number of balloon inflations and the inflation time and pressure were similar in symptomatic and asymptomatic patients. In each group, no short-term variability of baseline beta-endorphin plasma levels was observed during 2 consecutive days. Corresponding beta-endorphin plasma levels (at baseline and during and after angioplasty) were significantly higher in Group 2. During balloon occlusion, the levels decreased significantly in the symptomatic group at the onset of angina but remained stable in the asymptomatic group., Conclusions: Methodologic variables and the severity of coronary artery disease did not influence the presence of symptoms during angioplasty-induced ischemia. Beta-endorphin plasma levels were higher and more stable in patients with silent ischemia during angioplasty, suggesting that opiate levels and their variation during ischemia are associated with individual attitude toward anginal pain.

The elastic behavior of the dilated coronary vessel has been reported to affect the immediate results of coronary angioplasty. To determine whether elastic recoil may also influence the long-term restenosis process, 98 consecutive patients with unstable angina and 1-vessel disease were studied. An automated coronary quantitative program was used for the assessment of balloon and coronary luminal diameters. Elastic recoil was defined as the percent reduction between minimal balloon diameter at the highest inflation pressure and minimal lesion diameter immediately after coronary angioplasty. Follow-up coronary arteriography was performed 8 to 12 months after the procedure in all patients. The mean elastic recoil averaged 17.7 +/- 16% and was correlated to the degree of residual stenosis immediately after coronary angioplasty (r = 0.64; p < 0.001). Restenosis, defined as > 50% diameter stenosis at follow-up, developed in 53 patients (54%). There was no correlation between the degree of elastic recoil and the changes in minimal lesion diameter observed during follow-up, whereas a positive correlation between the amount of elastic recoil and the incidence of restenosis was documented (r = 0.84; p < 0.05). Thus, the elastic properties of the dilated vessel do not influence the active process of restenosis. However, because elastic recoil negatively influences the initial results of angioplasty, it is more likely that further reductions in lumen diameter during follow-up can reach a threshold of obstruction considered critical for a binary definition of restenosis.

Congestive heart failure represents the most common medical hospital discharge diagnosis, and can occur in patients with preserved indexes of left ventricular systolic function, even in absence of patent coronary or valvular heart disease. The present review examines the role of imaging techniques in the diagnosis and follow-up of these patients. Imaging of the heart has undergone dramatic advances with the development and refinement of new imaging modalities such as echocardiography, computed tomography, magnetic resonance and radionuclide emission tomography. The role of "low-tech" modalities such as chest roentgenogram is discussed. The possibilities offered by ultrasounds or magnetic resonance in tissue characterization are then compared with the actual capability of cardiac imaging in detecting myocardial tissue alterations (oedema, ischemia, myocarditis, etc.) and/or degeneration (fatty degeneration, fibrosis, amyloidosis, etc.). Finally, the potential use in modern clinical medicine of magnetic resonance spectroscopy and positron emission tomography to study myocardial metabolism and cellular function are discussed.

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.

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)

The purpose of this study was to evaluate the hemodynamic benefits of atrioventricular (A-V) sequential pacing. 30 pts implanted with DDD pacemakers underwent M-mode, B-mode and Doppler echocardiography. In each patient, left ventricular (LV) stroke volume was assessed by measuring the time-velocity integral of mitral inflow in the following modes and rates: VOO at 70 ppm or at the minimum stimulation rate and at 120 ppm; DOO at the same rates with different A-V delay (100, 150, 200, 250 and, whenever possible, 300 msec). The increase in stroke volume obtained with dual chamber pacing at the optimal A-V delay was 45 +/- 25% at 75 ppm and 29 +/- 14% at 120 ppm (p less than 0.05 75 vs 120 ppm). This increase was significantly higher in pts with than in pts without LV hypertrophy (respectively: 51.9 +/- 20.4 vs 36.9 +/- 20.8% at 75 ppm, p less than 0.05 and 33 +/- 13.4 vs 25.4 +/- 14.5% at 120 ppm, p = 0.08). Concerning the A-V delay, we noted that at 75 ppm stroke volume was significantly higher in DOO than in VOO with any A-V delay ranging +/- 100 msec from the optimal one; at 120 ppm the hemodynamic benefit of DOO pacing was observed only when the programmed A-V delay was the optimal one or very near to it. In conclusion, atrio-ventricular sequential pacing allows a significant increase in LV stroke volume over single chamber ventricular pacing both at 75 and 120 ppm. Programming the optimal A-V delay is absolutely necessary to obtain this hemodynamic benefit at the higher stimulation rate.

The continuity equation, applied to the flow convergence region (FCR), fournishes a simple alternative to calculate stenotic valve area. The flow rate in the FCR can be calculated by multiplying the hemispheric isovelocity surface area by the velocity of the isovelocity surface. Since according to the continuity principle the flow rate through any isovelocity surface equals the flow rate through the stenotic orifice, the stenotic orifice area can be calculated as: 2 pi r2Vr/Vm, where 2 pi r2 is the hemispheric isovelocity area, Vr is the velocity at the radial distance r from the orifice and Vm is the peak jet velocity. This study was designed to analyze the validity of application of the continuity equation to the FCR for estimating mitral orifice area by Dopler ultrasound. We studied 35 consecutive patients with rheumatic mitral stenosis. Three patients were excluded; the final study population consisted of 32 patients (8 men and 24 women; mean age 56 years). Nine patients were in normal sinus rhythm and 23 in atrial fibrillation. Doppler examination was performed from the apical approach within 24 hours of cardiac catheterization. On color Doppler image Vr was defined as the first aliasing limit (lowered to 38 cm/s to increase FCR r); r represented the maximal early diastolic distance between the first alias and the stenotic orifice in a direction parallel to that of the transducer; Vm was the early diastolic peak jet velocity by continuous wave Doppler.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

In prosthetic or paravalvular prosthetic mitral regurgitation, transthoracic color Doppler flow mapping can sometimes fail to detect the regurgitant jet within the left atrium because of the shadowing by the prosthetic valve. To overcome this limitation, we assessed the utility of color Doppler visualization of the flow convergence region (FCR) proximal to the regurgitant orifice in 20 consecutive patients with mechanical prosthetic mitral regurgitation documented by surgery and cardiac catheterization (13 of 20 patients). In addition, we studied 33 patients with normally functioning mitral prostheses. Doppler studies were performed in the apical, subcostal, and parasternal long-axis views. An FCR was detected in 95% (19 of 20) of patients with prosthetic mitral regurgitation. A jet area in the left atrium was detected in 60% (12 of 20) of patients. In 18 of 19 patients with Doppler-detected FCR, the site of the leak was correctly identified by observing the location of the FCR. A trivial jet area was detected in eight patients with a normally functioning mitral prosthesis; in none was an FCR identified. Thus color Doppler visualization of the FCR proximal to the regurgitant orifice is superior to the jet area in the diagnosis of mechanical prosthetic mitral regurgitation. Moreover, FCR permits localization of the site of the leak with good accuracy.

We thought chest pain associated with ST segment elevation during exercise test in patients with not significant coronary lesions could be related to coronary spasm. Three patients with mild coronary obstructive lesions underwent coronary arteriography during exercise test. In two patients this hypotesis was supported by angiographic documentation of the coronary spasm.

Left ventricular pseudoaneurysm is a rare condition which may develop after rupture of the ventricular myocardial wall. A localized hemopericardium confined is then formed outlined by the parietal pericardium. The pseudoaneurysmal sac is formed by clots and fibrous pericardial tissue and is directly connected to the ventricular chamber. There are no specific clinical signs to identify the disease. Two dimensional echocardiography and computerized tomography can allow the correct diagnosis to be made before cardiac catheterization. Two cases of left ventricular pseudoaneurysm occurring one after chest trauma and the other after acute myocardial infarction are reported.

This report addresses the problems related to surgical treatment of post-infarction ventricular tachycardia (VT) and is based on a 5 year experience of 36 consecutive patients. In every case the arrhythmia was unresponsive to pharmacological therapy. All patients were operated on after the completion of a diagnostic protocol including preoperative endocardial, intra-operative epi-endocardial mapping, the latter performed automatically when possible. Surgical techniques were: classical Guiraudon's encircling endocardial ventriculotomy (EEV); partial EEV, endocardial resection (ER); cryoablation or a combination of these procedures. The in-hospital mortality (30 days) was 8.3% (3 patients). During the follow-up period (1-68 months), 3 patients (9%) died of cardiac but not VT related causes. Of the survivors, 92% are VT-free. We consider electrophysiologically guided surgery a safe and reliable method for the treatment of post-infarction VT and suggest its more extensive use. We stress the importance of automatic mapping in pleomorphic and non-sustained VT, and the necessity of tailoring the surgical technique to the characteristics of each case.

Five patients affected by angina pectoris showed a spontaneous attack of myocardial ischemia in the course of coronary arteriography examination. During the ischemic episode it was shown a severe coronary arterial spasm promptly relieved by nitroglycerin. In these patients the administration of ergonovine maleate induced the same clinical, electrocardiographic and coronariographic patterns of spontaneous ischemic episodes. These data support the hypotesis that the ergonovine maleate administration is a suitable test for detection of the vasospastic pathogenesis in acute myocardial ischemia.

The effects of isometric exercise on left ventricular function in 16 patients with chronic coronary heart disease were assessed by measuring left ventricular pressures and volumes under basal conditions and during a sustained effort of 2 minutes 30 seconds at 50% of the maximal effort. In 7 patients (Group I) with abnormal elevation of left ventricular end diastolic pressure (LVEDP) (over 4 mmHg) the end diastolic volume remained unchanged and the diastolic pressure-volume curve was displaced upwards. The ejection fraction fell together with the percentage filling during the first part of diastole with 50% filling occurring after 61% instead of 45% of diastole. The time constant T also increased showing abnormal relaxation. In 9 patients without abnormal elevation of LVEDP on exercise no changes in the other parameters studies were observed. Our results show that pathological elevation of LVEDP during isometric exercise is associated with a decreased ejection fraction and an abnormality of left ventricular relaxation with a reduced rate of filling during protodiastole and an upward displacement of the diastolic pressure-volume curve. The LVEDP alone is therefore an important index of the haemodynamic behaviour of the left ventricle during isometric exercise.

Ergonovine testing was carried out in a selected group of 25 patients with Prinzmetal's variant angina treated with calcium-antagonists in order to: define its usefulness in the evaluation of the short-term effectiveness of calcium-antagonist treatment; compare the results of the test with those of Holter monitoring; verify if the results of the test during the acute phase are correlated with the long-term response to treatment. In all patients a control period lasting 2-6 days was carried out, after which a treatment period with calcium-antagonists (nifedipine, diltiazem, verapamil), lasting 2-8 days, was instituted. In 20 patients only 1 calcium-antagonist was evaluated, in 1 patient 2 calcium-antagonists and in 4 all of them. Scalar ergonovine test was carried out in control conditions and repeated during each calcium-antagonist treatment period. During both control and treatment periods all patients underwent Holter monitoring for evaluation of frequency of the spontaneous attacks. After the acute phase 21 of the 25 patients were discharged on calcium-antagonist treatment and followed-up for a mean period of 11 +/- 7 months. In control conditions ergonovine test was positive in 24 patients at a mean dose of 0.11 +/- 0.09 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

30 patients with a previous myocardial infarction who had undergone diagnostic conventional left ventriculography and coronary arteriography had left ventriculography also performed by digital subtraction angiography after intravenous injection of contrast medium; the mean interval between the two investigations was 2.3 days. The conventional and the digital subtracted left ventricular images were computer-processed; global ejection fraction (obtained by the volumes calculated with the Dodge method) and segmental wall motion (from a quantitative analysis performed according to the Stanford method) were compared. We found a close correlation for the ejection fraction obtained by the two techniques (r = 0.89, p less than 0.01); absolute values proved to be slightly higher in the digital subtraction angiography. Segmental wall motion was significantly correlated too (p less than 0.05 for all the segments of the ventricular silhouette but for the one corresponding to the base of the heart). Digital intravenous angiography provides an accurate and less invasive method to evaluate left ventricular function.

Unlabelled: To investigate the incidence of myocarditis, 30 patients, with unexplained congestive heart failure, underwent endomyocardial biopsy. For each case three to five samples were examined on light and electron microscopy. Inflammatory infiltrates and injury to adjacent myocytes consistent with myocarditis were detected in 3 of the 30 cases (10%). Changes attributable to cardiomyopathy were found in the remaining 27 cases. Two of the three patients with biopsy-proven myocarditis were treated with prednisone and azathioprine. Their control biopsies six months later showed interstitial fibrosis and absence of inflammatory infiltrates. They clinically improved but hemodynamic and angiocardiographic patterns failed to show the expected improvement. The third patient affected by myocarditis died two weeks later., In Conclusion: in our series of patients with unexplained congestive heart failure, the incidence of biopsy-proven myocarditis resulted low (10%). The results of the immunosuppressive treatment in two patients with myocarditis were unconclusive. Therefore the effectiveness of such therapy should be confirmed in a larger number of patients.

The purpose of this study was to delineate the clinical, ECG, and angiographic features of a large series of consecutive patients with angina at rest. Transient ST segment elevation during pain was observed in 219 patients (group I), while 220 patients showed ST segment depression during pain (group II). Group II patients were found to have higher incidence of hypertension (p less than 0.001), prior myocardial infarction (p less than 0.0005), history of exertional angina (p less than 0.0005), and a progressive aggravation of symptoms before hospitalization (p less than 0.0005), while group I patients had a prevalence of recent onset angina (p less than 0.05) and more frequently developed severe ventricular arrhythmias during pain (p less than 0.0005). Furthermore, a larger number of patients showing ST segment depression during chest pain had multivessel disease (p less than 0.0005), left main involvement (p less than 0.005), and lower values of left ventricular ejection fraction (p less than 0.001) than patients with ST segment elevation during pain. Survival curves of medically treated patients showed a significantly better long-term prognosis in patients of group I (p less than 0.01). The direction of the ST segment shift during anginal attacks at rest may therefore allow a classification of patients included into the broad spectrum of unstable angina. This distinction should be taken into consideration in studies aimed at evaluating long-term prognosis or the results of medical and surgical therapy.

Thirty patients with myocardial infarction were studied using Digital Subtraction Ventriculography with Intravenous injection (DSVIV) between 3 and 6 days from myocardial infarction and were checked after 30 and 90 days. The variation of ejection fraction in the controls was not important. The wall motion provided precise indications regarding the infarctual regions. Digital subtraction ventriculography seems to be a very interesting tool in the study of the left ventricle in the evolution of myocardial infarction, thanks to a low invasivity, providing data on ventricular function.