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.

Susceptibility to pain during coronary angioplasty: usefulness of pulpal test.

OBJECTIVES: This study in patients with coronary artery disease (CAD) sought to 1) determine the dental pain threshold and reaction to tooth pulp stimulation; 2) correlate the clinical, ergometric and angiographic features of patients with and without pain during percutaneous transluminal coronary angioplasty (PTCA) to pulpal test response; 3) verify whether reactivity to dental pulp stimulation could help to identify patients particularly prone to perceiving angina during myocardial ischemia. BACKGROUND: Silent myocardial ischemia is frequently observed in patients with CAD. Higher pain thresholds have been documented in asymptomatic subjects, suggesting a generalized hyposensitivity to pain. METHODS: Eighty-six consecutive male patients with reproducible exercise-induced myocardial ischemia and CAD documented by angiography underwent PTCA. A pulpal test was performed in all patients by means of an electrical tooth pulp stimulator. RESULTS: Seventy-one patients (82.6%) with and 15 (17.4%) without angina during daily life were studied. During the pulpal test, 57 patient (66.2%) reported dental pain, whereas 29 (33.7%) were asymptomatic, even at maximal stimulation of 500 mA. The study cohort was classified into two groups according to the presence (58 patients [group 1]) or absence (28 patients [group 2]) of angina during myocardial ischemia induced by PTCA. Ergometric variables, extent of CAD, presence of ST segment elevation during PTCA, number of inflations, inflation time and maximal inflation pressure were similar in the two patient groups. Dental pain was provoked by pulpal test in 81% of patients with and 36% of patients without symptoms during PTCA (p = 0.0004). The absence of dental pain even at maximal tooth pulp stimulation (500 mA) was observed in 11 (18.9%) patients in group 1 and 18 (64.2%) in group 2. Patients who were asymptomatic during PTCA had a higher mean dental pain threshold, lower mean threshold reaction and lower mean maximal reaction than those who were symptomatic during both PTCA and the pulpal test. CONCLUSIONS: A correlation between the prevalence of symptoms during pulpal test, daily life, exercise-induced myocardial ischemia and PTCA was found. A higher dental pain threshold and lower reactivity characterized those subjects who were prone to silent ischemia both during daily life and during PTCA. Ergometric variables, extent of CAD and techniques used during PTCA were unrelated to the tendency to perceive pain during myocardial ischemia. Response to the pulpal test and the presence of symptoms during daily life were highly related to the presence of angina during PTCA.

Thrombin activity and early outcome in unstable angina pectoris.

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.

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.

[Results and prognostic significance of echocardiography-dobutamine + atropine test in recent non-Q wave myocardial infarction]. / Risultati e significato prognostico del test eco-dobutamina + atropina nell'infarto miocardico non-Q recente.

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.

[A measure of productivity in cardiology based on medical acts]. / Una misura di produttività in cardiologia basata sugli atti medici.

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.

Efficacy and pharmacokinetics of simvastatin in heart transplant recipients.

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.

[The side effects and safety of the echo-dobutamine test. The experience with 373 patients]. / Effetti collaterali e sicurezza del test eco-dobutamina. Esperienza in 373 pazienti.

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.

[Recovery time from myocardial ischemia induced by exercise test: correlation with duration of ischemia during the test and with the extent of coronary disease]. / Tempo di recupero dall'ischemia miocardica indotta mediante test da sforzo: correlazione con la durata dell'ischemia durante il test e con l'estensione della malattia coronarica.

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.

[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.

Comparative trial of quinapril versus captopril in mild to moderate congestive heart failure. Quinapril/Captopril Congestive Heart Failure Study Group.

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.

[Percutaneous approach in the use of subclavian vein in pacemaker implantation]. / Utilizzo della vena succlavia per via percutanea per impianto di pacemaker.

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.

[The ergometric test after a heart transplant: its usefulness and limits]. / Test ergometrico dopo trapianto cardiaco: utilità e limiti.

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)

[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.

[Different susceptibilities to the development of nitroglycerin tolerance in the human peripheral venous and arterial circulations]. / Differente suscettibilità allo sviluppo di tolleranza alla nitroglicerina nella circolazione venosa ed arteriosa periferica dell'uomo.

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.

[Coronary vasomotor response to acetylcholine correlates with plasma levels of cyclosporin and triglycerides in patients with heart transplantation]. / La risposta vasomotoria coronarica all'acetilcolina si correla con i livelli plasmatici di ciclosporina e trigliceridi nei pazienti cardiotrapiantati.

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.