[The acute and chronic effects of 10-mg nitroglycerin patches in stable angina of effort]. / Estudio del efecto agudo y crónico de los parches de 10 mg de nitroglicerina en la angina de esfuerzo estable.

INTRODUCTION AND OBJECTIVES: To assess the anti-ischemic efficacy of nitroglycerin patches (10 mg/day), we studied, by means of serial exercise testing (Bruce protocol), 10 patients with stable effort angina in a randomized, placebo-controlled, cross-over, double-blind essay. METHODS: Patients were exercised 1, 4, 12 and 24 hours after a single patch, and 4 and 12 hours after a 48 hours therapy course. Chronic therapy was assessed after both continuous and intermittent (intermission of 12 hours) patch application. RESULTS: After single patch, time to angina and time to 1 mm ST depression were significantly increased with respect to placebo at 1-hour test (83 +/- 27 s and 119 +/- 39 s, respectively), 4-hour test (100 +/- 34 s and 87 +/- 29 s, respectively) and 12-hour test (46 +/- 15 s and 64 +/- 20 s, respectively). No effect was demonstrated at 24-hour test. After continuous treatment no differences with respect to placebo were found at any test. After intermittent treatment time to angina was prolonged (75 +/- 23 s) only at 4-hour test, and time to 1 mm ST depression at 4-hour test (61 +/- 19 s) and 12-hour test (41 +/- 14 s). CONCLUSIONS: Nitroglycerin patches improve parameters of exercise ischemia for a 12 hours period. Tolerance is developed very early and provokes absolute lack of efficacy. Tolerance can be avoided with intermittent patch application. No treatment schedule shows 24 hours efficacy.

Comparison of acute and steady-state conditions of gallopamil therapy in stable angina pectoris.

We studied 12 patients with stable effort angina in a randomized, double-blind, cross-over and placebo-controlled trial to compare the different antianginal efficacy of "acute" and "chronic" (after reaching a steady-state level) gallopamil therapy. Efficacy was assessed using treadmill exercise testing (Bruce protocol) after a 50 mg single-dose and at the end of a nine-dose course of 50 mg of gallopamil (given three times a day). Three daily exercise tests were performed the first, second, fifth and eighth day of the study protocol at 8, 12 and 16 h. Four hours after a single-dose of gallopamil 50 mg both angina-free exercise time and time to 1 mm ST segment depression increased by a mean value of 78 s (p < 0.003) and 53 s (p < 0.03), respectively, with respect to placebo values. Under steady-state conditions exercise time and time to 1 mm ST segment depression increased by a mean value of 59 s (p < 0.009) and 46 s (p < 0.015), respectively, 4 h after the last dose. The duration of the anti-ischemic effects was no longer present after 8 h for both treatment schedules. Furthermore no significant differences were observed on parameters of ischemia after a single dose as compared to "chronic" therapy. The results of this study reveal that, in accordance with the pharmacodynamic properties of the drug, the anti-ischemic efficacy of 50 mg of gallopamil remains for approximately 4 h. Reaching a steady-state condition does not imply a prolongation of the anti-ischemic effect.

Differences in response to single dose and steady-state therapy with verapamil in stable angina.

Ten patients with stable effort angina were studied in a randomized double-blind and placebo-controlled trial to compare the antianginal efficacy of "acute" and "chronic" (after reaching a steady-state level) treatment with verapamil. Efficacy was assessed by exercise testing after a 120 mg single-dose and at the end of a seven-dose course of 120 mg of verapamil given thrice daily. Three daily exercise tests were performed the first, second and fifth day of the study protocol at 8, 12 and 16 hours. Eight hours after the last dose was given, exercise time increased by 54 +/- 30 sec after a single-dose of verapamil and by 156 +/- 31 sec after seven-doses of verapamil (P less than 0.05 as compared to single-dose verapamil). The time to 1 mm depression of the ST segment increased by 30 +/- 20 sec after a single-dose of verapamil and by 66 +/- 28 sec after seven-doses of verapamil (P less than 0.01 as compared to single dose verapamil). Six of the ten patients became free from angina on treadmill exercise after a seven-dose course of verapamil, but only one patient became free from angina after acute testing with a single-dose of verapamil. It is concluded that several doses of verapamil are required to achieve an optimal anti-ischemic effect, as suggested by the pharmacodynamic properties of this drug. Once steady-state is achieved, the effects of verapamil remain for at least 8 hours, so that an administration schedule of three times daily protects the patient for a 24-hour period.

[Factors affecting early graft patency after coronary grafts]. / Factores que influyen en la permeabilidad precoz de los injertos coronarios.

From June 1984 to December 1987, an early postoperative angiographic study was performed in 247 patients who underwent isolated coronary artery bypass surgery. The average age of these patients was 58.6 years, range 31 to 75 years. Preoperatively 50.8% of patients had myocardial infarction and 43.2% of them had unstable angina before surgery. Early coronary artery bypass angiogram was performed in 683 grafts (2.76 grafts per patient): 74 internal mammary artery grafts and 609 saphenous vein grafts. The distribution, location and type of the stenosis, distal coronary artery diameter, segmental myocardial contractility, and distal angiographic coronary filling are analyzed with a matching statistical method. Multivariate analysis showed significant predictors of early graft occlusion to be right coronary and circumflex artery, poor or non visible distal angiographic filling, coronary arteries smaller than 1.5 mm. The univariate analysis associates as risk factors hypokinetic or akinetic territories and multiple stenosis coronary arteries. It can be concluded that the early angiographic study demonstrate that coronary arteries with multiple stenosis, poor distal angiographic filling, smaller than 1.5 mm in diameter, coronary arteries perfusing hypokinetic or akinetic territories and the right coronary and left circumflex artery grafts have significantly lower early cumulative patency rates.

Prevention of early aortocoronary bypass occlusion by low-dose aspirin and dipyridamole. Grupo Español para el Seguimiento del Injerto Coronario (GESIC)

To analyze the efficacy of low-dose aspirin in preventing early aortocoronary vein graft occlusion, 1,112 consecutive patients were enrolled in a multicenter, randomized, double-blind, placebo-controlled trial comparing 50 mg t.i.d. aspirin, 50 mg aspirin plus 75 mg t.i.d. dipyridamole, and placebo. All patients received 100 mg q.i.d. dipyridamole for 48 hours before surgery, and assigned treatment was started 7 hours after surgery. Vein graft angiography was performed in 927 patients (83%) within 28 days of surgery (mean, 10 days). Aspirin plus dipyridamole significantly (p = 0.017) reduced the occlusion rate of distal anastomoses from 18% (placebo) to 12.9%. Occlusion rate in the aspirin group was 14%, which approached statistical significance (p = 0.058). Furthermore, only aspirin plus dipyridamole reduced (p = 0.01) the number of patients with occluded grafts (placebo, 33%; aspirin, 27.1%; aspirin plus dipyridamole, 24.3%). Mediastinal drainage was slightly higher (p = 0.04) in the aspirin plus dipyridamole group (713 +/- 456 ml) than in the other two groups (placebo, 670 +/- 437 ml; aspirin, 629 +/- 337 ml), but hospital mortality (average, 4.6%) and early reoperation (average, 3.9%) rates were similar among the three groups. Thus, low-dose aspirin plus dipyridamole safely improves early saphenous vein aortocoronary graft patency; this effect is an added benefit to a preoperative regimen of dipyridamole.

[Evaluation using serial exercise tests of verapamil alone and combined with isosorbide dinitrate in exertional angina]. / Valoración mediante pruebas de esfuerzo seriadas del verapamil solo y combinado con dinitrato de isosorbide en la angina de esfuerzo.

The response to verapamil alone and combined with isosorbide dinitrate in a group of 12 patients with severe ischemic heart disease and stable effort angina was assessed by means of serial treadmill testing. The study was randomized, of a square latin design and double-blind. The tested drugs and dosages were 120 mg of verapamil, 120 mg of verapamil plus 20 mg of isosorbide dinitrate and placebo. Patients were serially tested (Bruce protocol) over three consecutive days at 8-9-12 and 16 hours. A significative improvement was observed in several ischemic parameters both with verapamil alone and combined with isosorbide dinitrate, but this improvement was remarkably enhanced with the combination of drugs. The mean exercise time to produce angina improved from 268 +/- 18 sec (basal) to 379 +/- 19 sec (verapamil plus isosorbide dinitrate) and the time for 1 mm ST segment depression from 163 +/- 22 sec (basal) to 257 +/- 19 sec (verapamil plus isosorbide dinitrate) when measured at the last daily test (8 hours after drug administration). It is concluded that both verapamil alone and combined with isosorbide dinitrate at the chosen doses are clinically efficient, significantly improving the ischemic parameters. The combination of verapamil and isosorbide dinitrate resulted in a remarkably better improvement in this group of patients with stable effort angina.

An assessment of single doses of 8 mg sustained-release molsidomine using serial exercise tests.

The effectiveness and duration of the anti-anginal action of two sustained-release preparations, molsidomine (8 mg) and isosorbide dinitrate (20 mg), were assessed by means of serial exercise tests in 12 patients with angina of effort. The tests, which were limited by the symptoms, were carried out on three consecutive days using the Bruce protocol. Each patient was tested four times each day: the first test was performed before treatment and the others were carried out 1, 4 and 8 h after administration of the drug or placebo. One hour after administration of molsidomine, the appearance of signs of ischaemia in the ECG were considerably delayed and they were reduced in magnitude. Furthermore, the length of time during which the patients were free of angina increased. After 4 h both drugs significantly delayed the onset of angina and depression of the ST segment by 1 mm. The conclusion is that at the doses used both drugs prolong the length of time in which there is no angina, but that they have no significant effect at 8 h.

Comparison of Doppler-determined elevated pulmonary arterial pressure with pressure measured at cardiac catheterization.

This study assesses use of pulsed Doppler echocardiography to measure pulmonary artery (PA) pressure. PA flow at the right ventricular (RV) outflow tract was analyzed in 51 patients. Attention was focused on PA flow morphologic pattern, RV systolic intervals, time to peak flow and acceleration time index. Correlation was made with PA pressure and total pulmonary resistance. Three morphologic patterns of PA flow were found: type I indicates normal PA pressure (sensitivity 85%, specificity 100%) and types II and III indicate PA hypertension (sensitivity 100%, specificity 85%). The RV preejection/RV ejection ratio, time to peak flow and acceleration time index show a good correlation coefficient improved when a logarithmic function was applied. The best correlation was achieved with time to peak flow (r = -0.77 with PA pressure, r = -0.79 with total pulmonary resistance), and especially with acceleration time index (r = -0.84 with PA pressure, r = -0.87 with total pulmonary resistance). Analysis of pulmonary flow is a reliable new tool for evaluating PA pressure and is even better for evaluating total pulmonary resistance. Acceleration time index is the parameter that correlates best with these 2 variables.

Coronary arteriography and atrial thrombosis in mitral valve disease.

The arteriographic findings of neovascularity and fistula formation from the coronary arteries to the left atrium have occasionally been reported in association with atrial thrombosis in patients with mitral valve disease. To establish the diagnostic value of these findings, the preoperative coronary angiograms of 507 patients who underwent open mitral valve surgery were reviewed. Atrial thrombosis was present in 76 patients (14.9 percent). In the 30 patients with angiographic neovascularity and fistula formation, the thrombi were always observed to arise from the circumflex coronary artery. None of these 30 patients had atherosclerotic coronary lesions. In 25 of these patients an atrial thrombus was found at operation. These coronary arteriographic findings, in this selected group of patients, had a predictive accuracy of 83.3 percent, a specificity of 98.8 percent and a sensitivity of 32.8 percent for the diagnosis of the presence of thrombus in the left atrium. No relation was found between these signs and the size and histologic age of the thrombi examined.