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Background: Before any new diagnostic test is accepted in clinical practice, such a test should be compared with established diagnostic tools in an appropriately large series of patients encompassing the complete spectrum of challenges to which the test is exposed. The aim of the present study was to assess the relative diagnostic and prognostic accuracies of high-dose dipyridamole echocardiography (two-dimensional echocardiographic monitoring during dipyridamole infusion up to 0.84 mg/kg over 10 hours) versus maximal symptom-limited bicycle exercise ECG test in patients with angina., Methods and Results: We studied 429 consecutive in-hospital patients who met the following inclusion criteria: history of chest pain, off antianginal therapy for at least 2 days (1 week for beta-blockers), no previous myocardial infarction and/or obvious regional left ventricular dyssynergy of contraction (akinesis or dyskinesis) at baseline, and acceptable acoustic window under resting conditions. All patients underwent dipyridamole echocardiography and exercise ECG--on different days and in random order--within 1 week of coronary angiography (which was performed independent of test results) and were followed up for 37.8 +/- 14 months (range, 1 to 73 months). Criteria of positivity were for dipyridamole echocardiography, a transient regional dyssynergy absent in the baseline examination; for exercise ECG, an ST-segment shift of > or = 0.1 mV from baseline; and for coronary angiography, a luminal reduction of > or = 75% in at least one major coronary vessel (50% for left main). There were 183 patients without and 246 with coronary artery disease; 132 had one-, 70 had two-, and 44 had three- and/or left main vessel disease. The specificity was higher for dipyridamole echocardiography than for exercise ECG (90% versus 51%, P < .001). The overall sensitivity of dipyridamole echocardiography was similar to that of exercise ECG (75% versus 74%, P = NS), with no significant differences in the subset with one- (67% versus 69%, P = NS), two- (79% versus 77%, P = NS), or three- (93% versus 86%, P = NS) vessel disease. During the follow-up, there were 20 deaths, 13 nonfatal myocardial infarctions, and 126 revascularization procedures. In the univariate analysis, dipyridamole resulted in higher chi 2 values than did exercise stress testing. A Cox forward stepwise survival analysis identified the dipyridamole time as the most powerful prognostic predictor of death (chi 2 = 19.4, P < .0001) of all invasive and noninvasive parameters. The dipyridamole time also provided independent and additional prognostic information when it was adjusted for age, diabetes, resting ECG, and exercise stress test according to a modified, interactive stepwise procedure. This is true when death only, death and myocardial infarction, and death, myocardial infarction, and revascularization procedures were considered end points., Conclusions: In patients with no previous myocardial infarction and good resting left ventricular function, compared with exercise ECG, dipyridamole echocardiography has a similar sensitivity and a higher specificity for the noninvasive detection of angiographically assessed coronary artery disease. Dipyridamole echocardiography also provides information in addition to that provided by exercise ECG for predicting death, infarction, and all events when the presence as well as the timing, severity, and extension of dipyridamole-induced wall motion abnormalities are considered.

Objectives: This study was conducted to assess the feasibility, safety and prognostic value of dipyridamole echocardiography in elderly patients recovering from an uncomplicated acute myocardial infarction in a subset analysis performed on the patients entered in the subproject "residual ischemia" of the Echo Persantine Italian Cooperative Study (EPIC)., Background: Coronary heart disease accounts for two thirds of all deaths in the age group > 65 years, and > 50% of all patients admitted to the hospital with acute myocardial infarction are > 65 years old. The prognostic value of dipyridamole-induced left ventricular dysfunction was clearly established in patients evaluated early after acute infarction., Methods: In a subgroup analysis of the Echo Persantine Italian Cooperative Study (EPIC), we assessed the value of dipyridamole echocardiography in predicting cardiac events in 190 elderly (> or = 65 years) patients (age 68.4 +/- 3.3 years, range 65 to 78; 147 men and 43 women) evaluated early (mean 10 days) after uncomplicated acute myocardial infarction and followed up for 14 +/- 9.8 months., Results: There was no major side effect during dipyridamole echocardiography. A positive test result occurred in 85 patients (44.7%). During follow-up, there were 62 events (14 cardiac deaths, 7 nonfatal reinfarctions, 21 cases of class III or IV angina and 20 revascularization procedures). Of these 62 events, 44 occurred among 85 patients with positive dipyridamole echocardiography and 18 among 105 patients with negative dipyridamole echocardiography (52% vs. 17%, p < 0.001). Spontaneous events (death, reinfarction, angina) occurred in 31 patients with positive and in 11 with negative dipyridamole echocardiography (36% vs. 10%, p < 0.001). Hard events (myocardial infarction or death) occurred in 14 patients with positive and 7 with negative dipyridamole echocardiography (16% vs. 6%, p < 0.05). Death occurred in 11 patients with positive and in 3 with negative dipyridamole echocardiography (13% vs. 3%, p < 0.01). The positive predictive value of positive dipyridamole echocardiography and negative predictive value of negative dipyridamole echocardiography as related to the occurrence of all events in the follow-up period (death, reinfarction, angina, revascularization procedures) were 52% and 83%, respectively. The relative risk (that is, the relative risk of occurrence of future cardiac events in the group with positive dipyridamole echocardiography compared with that in those with negative dipyridamole echocardiography) was 3 for all events and 4.4 for death., Conclusions: Dipyridamole echocardiography was well tolerated by elderly patients and proved to be very effective in prognostic stratification early after uncomplicated acute myocardial infarction, even when only survival was considered.

This study was designed to assess the efficacy of oral nifedipine as compared to oral isosorbide-5-mononitrate in the prevention of spontaneous and induced vasospastic myocardial ischaemia. Twenty-one patients admitted to the Coronary Care Unit as a result of angina at rest underwent both Holter monitoring and an echo-ergonovine test during placebo and following either isosorbide-5-mononitrate or nifedipine according to a double-blind randomized trial. Both drugs caused a statistically significant reduction in spontaneous (87% and 95%, respectively) and induced ischaemic attacks (66% and 75%, respectively). No significant difference was found between the two drugs.

Objectives: The aim of the study was to evaluate the relation between measurements derived from myocardial contrast echocardiography and coronary blood flow., Background: Contrast echocardiography has the potential for measuring blood flow., Methods: In six open chest anesthetized dogs, the left circumflex coronary artery was cannulated and perfused with blood drawn from the left femoral artery. While adenosine was infused into the circuit, circumflex flow was generated by a calibrated roller pump to the point of abolishing coronary autoregulation. At each of 25 levels of coronary blood flow, paired bolus injections of sonicated iopamidol were performed proximal to a mixing chamber. The perfused area of the left circumflex coronary artery was labeled by radioactive microspheres injected into the perfusion line. Two-dimensional echocardiographic images of the left ventricular short axis were digitized off-line, and myocardial videodensity was measured in the area perfused by the left circumflex coronary artery to generate time-intensity curves., Results: The washout slope of curves showed a good correlation with coronary blood flow, ranging from 0.5 to 12.5 ml/min per g of tissue. This correlation was good both in individual dogs (correlation coefficient [r] ranging from 0.78 to 0.96) and in the group of animals as a whole (r = 0.85). Washout slope also showed a good correlation with coronary diastolic pressure (r = 0.80), which ranged from 23 to 114 mm Hg, suggesting a possible primary effect of pressure on contrast washout. However, coronary blood flow appeared to be a stronger predictor of washout slope (partial F = 26.5, p < 0.001) than did perfusion pressure (partial F = 5.9, p < 0.05 by multiple regression). The injection to injection variability in myocardial washout slope appeared to be high (24%). The gamma variate fitting of curves did not improve the correlation with coronary flow (r = 0.78)., Conclusions: Myocardial washout of sonicated iopamidol reflects coronary blood flow in a model in which coronary autoregulation is abolished.

Background: Any new diagnostic test should follow a pathway similar to that of a new drug, from initial studies in highly selected populations under strictly controlled conditions, up to large scale multicenter trials more likely to represent the true performance of the test in the clinical arena., Aim of the Study: To evaluate the capability of prognostic stratification of high dose (up to 0.84 mg/kg over 10') dipyridamole-echocardiography test (DET) early after an acute myocardial infarction in a "phase IV" study, based upon 11 different echocardiographic laboratories, all with established experience in stress echo and fulfilling quality control requirements for stress echo readings., Study Population: Nine-hundred twenty five patients were evaluated after a mean of 10 days from an acute myocardial infarction and followed up for a mean of 14 months., Results: During DET, one major adverse reaction occurred, consisting of a prolonged ischemia resistant to aminophylline and nitrates, and progressing to small uncomplicated reinfarction. In 11 patients the lower dipyridamole dose (0.56 mg/kg over 4') gave limiting side effects. Patients were followed up for 14 +/- 9.9 months (range = 1.53). During the follow-up, there were 34 deaths and 37 non-fatal myocardial infarctions; 104 patients developed class III or IV angina, and 149 had coronary revascularization procedures (bypass or angioplasty). Considering all spontaneous events (angina, reinfarction and death), the most important univariate predictor was the result of DET (chi-square = 45.8). With a Cox analysis, echocardiographic positivity, age and sex were found to have an independent and additive value. Considering survival (and therefore death as the only event) age was the most meaningful parameter, followed by the Wall Motion Score Index during dipyridamole (chi-square = 12.1); among other parameters, the resting Wall Motion Score Index was a significant predictor of death. By Cox analysis, age (relative risk estimate = 1.02) and Wall Motion Score Index during dipyridamole (relative risk estimate = 14) showed an independent and additional prognostic value. In particular, considering death only, the event rate was of 2% in patients with negative DET, 4% in patients with high dose positive DET and 7% in patients with low dose positive DET., Conclusions: Dipyridamole echocardiography is feasible and safe early after uncomplicated myocardial infarction and allows an effective risk stratification on the basis of the presence, severity, extent and timing of the induced dyssynergy. In particular, the risk of death doubles in patients with high dose positivity and almost quadruples in patients with low dose positivity.

According to the Stewart-Hamilton equation flow is inversely related to the area under the time-concentration curve produced by the transit of a detectable indicator. To verify the applicability of this principle for contrast echocardiography, we bolus injected a saccharide echo contrast agent (0.8 ml) into an in vitro circulatory model at variable flow rates. Two-dimensional echo images were digitized, and curves demonstrating the ratio of videointensity over time were derived. As expected, flow was inversely related to the area under the curves (r = 0.93). To apply this principle to human coronary circulation, we bolus injected sonicated iopamidol (4 ml) into the normal left coronary artery of six patients at baseline and after intravenous administration of dipyridamole (0.84 mg/kg in 10 minutes). Echo images were digitized, and myocardial time-intensity curves were derived. The area under the curve after dipyridamole administration (210 +/- 128 gray level.sec) did not appear significantly different from that at baseline (177 +/- 80 gray level.sec). Thus a mismatch exists between contrast echo data obtained in vitro and in human coronary circulation.

Background: Coronary vasodilator reserve is reduced in some patients with a history of chest pain and angiographically normal coronary arteries. ECG changes suggestive of myocardial ischemia during exercise also can be demonstrated in a subset of these patients., Methods and Results: We have investigated the correlation between coronary vasodilator reserve, assessed with 13N-labeled ammonia and positron emission tomography, and the ECG during exercise stress in 45 patients with a history of chest pain, angiographically normal coronary arteries, and a negative ergonovine test. ST segment depression on the ECG during exercise was present in 29 of 45 patients. Mean resting left ventricular blood flow was 1.04 +/- 0.22 ml.min-1.g-1; it increased to 1.32 +/- 0.47 ml.min-1.g-1 (p less than 0.01 versus baseline value) during atrial pacing and to 2.52 +/- 0.96 ml.min-1.g-1 (p less than 0.01 versus baseline value) after dipyridamole (0.56 mg/kg i.v.). No regional flow defects could be demonstrated in any patient during pacing or after dipyridamole. Myocardial flows after dipyridamole, however, did not show a normal frequency distribution (Kolmogorov-Smirnov test), and two patient populations could be identified. Twenty-nine (67%) patients had a mean left ventricular flow of 3.02 +/- 0.33 ml.min-1.g-1 after dipyridamole (range, 2.13-5.46 ml.min-1.g-1), and 14 (33%) patients had a mean flow of 1.48 +/- 0.29 ml.min-1.g-1 (range, 1.06-2.04 ml.min-1.g-1, p less than 0.01 versus the "high-flow group")., Conclusions: Approximately one third of patients in our series showed a reduced coronary vasodilator reserve. Although 12 of 14 patients in the "low-flow group" had ST segment depression during exercise stress, 16 of 29 patients in the high-flow group also had ST segment depression during exercise stress. Therefore, despite a good sensitivity (86%) in identifying patients with a blunted increment of coronary flow, the ECG response during exercise stress appears to have a rather low specificity (45%). This suggests that factors other than reduced coronary reserve and myocardial ischemia may play a role in the genesis of the ST segment depression in these patients.

This study evaluated the effect of pirenzepine, an M1 antimuscarinic agent, on exercise duration and ischemic threshold in patients with angiographically documented coronary artery disease and clear-cut ST depression (greater than 0.2 mV, 0.08 second after the J point) during ergometric stress testing. Twenty-five patients, mean age 56 +/- 8 years, underwent 3 randomized multistage bicycle exercise stress tests after intravenous administration of saline solution (2 ml), isosorbide dinitrate (1 mg) and pirenzepine (2 mg). Isosorbide dinitrate, an endothelium-independent coronary dilating agent, was used as a reference drug. Compared with saline, both pirenzepine and isosorbide dinitrate significantly improved time to ischemia (0.15 mV ST-segment depression) from 6.5 +/- 2 to 7.8 +/- 2 and 8.6 +/- 2 minutes and rate-pressure product at ischemia from 21,498 +/- 4,903 to 24,083 +/- 6,692 and 24,547 +/- 5,390 mm Hg.beats/min, respectively. Compared with saline, pirenzepine did not induce significant changes in blood pressure either at rest or during exercise, whereas it decreased resting heart rate from 71 +/- 9 to 60 +/- 11 beats/min (p less than 0.01) and induced a significant increment of heart rate during ischemia from 117 +/- 18 to 126 +/- 21 beats/min (p less than 0.05). Compared with saline, isosorbide dinitrate reduced systolic blood pressure at rest from 132 +/- 12 to 112 +/- 12 mm Hg, increased heart rate at rest from 71 +/- 10 to 84 +/- 16 beats/min and heart rate at ischemia from 117 +/- 18 to 132 +/- 16 beats/min.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of the study was to assess the relative diagnostic and prognostic accuracy of high-dose dipyridamole echocardiography test (DET: 2D-echo monitoring during dipyridamole infusion up to 0.84 mg/kg over 10') vs maximal symptom limited bicycle exercise electrocardiography test (EET) in patients with chest pain addressed to coronary angiography. We initially considered 477 consecutive patients, meeting the following inclusion criteria: 1) history of chest pain; 2) off antianginal therapy; 3) no previous myocardial infarction and/or obvious regional left ventricular dyssynergy of contraction. All patients were submitted to a DET and EET--on different days and in random order--within 1 week of coronary angiography (which was performed independently of test results). DET could not be performed in 32 patients for a poor acoustic window in resting conditions (n = 31) or for asthmatic disease requiring xanthine therapy (n = 1); EET could not be performed in 54 patients for inability to exercise, or resting electrocardiographic abnormalities making the EET interpretable. The overall feasibility was of 445/477 for DET and 423/477 for EET (93 vs 89%, p = ns). Criteria for positivity were: transient regional dyssynergy absent in the baseline examination for DET; ST segment shift greater than .15 m V from baseline for EET. Angiographically assessed coronary artery disease (CAD) was considered present when a luminal reduction greater than or equal to 50% occurred in at least 1 major coronary vessel. There were 135 pts with no significant CAD and 256 with CAD; 137 had single, 70 double, 49 triple and/or left main (15) vessel disease. The specificity was higher in DET vs EET (96 vs 59%, p less than .01). The overall sensitivity of DET was similar to EET (67 vs 69%, p = ns), with no significant differences in the subset with single (56 vs 63%, p = ns), double (74 vs 69%, p = ns) or triple (88 vs 86%, p = ns) vessel disease. Patients were followed-up for 26 +/- 22 (range 1 to 73) months considering only death and myocardial infarction as end-points. A Cox stepwise survival analysis identified the Wall Motion Score Index (an integrated semiquantitative measure of extent and severity of the dyssynergy) at peak dipyridamole as the most powerful prognostic predictor (X2 = 18.5, p less than 0001) of all invasive (number of stenotic coronary vessels, X2 = 5.8, p less than .05) and noninvasive (exercise electrocardiography positivity, p = ns) parameters.(ABSTRACT TRUNCATED AT 400 WORDS)

Observational data prospectively collected permit the examination of a complex set of decisions, including the decision not to perform any stress testing. Patients with or without previous myocardial infarction admitted for coronary evaluation and not submitted to any stress testing because of clinical reasons are at a higher risk for subsequent death. For prognostication, no test has been better validated than exercise electrocardiography: it can identify patients at low and high risk for future cardiac events among those without symptoms, with typical chest pain, and with previous myocardial infarction. In patients with triple-vessel disease, the results of exercise also allow those at low and high risk to be recognized. Both exercise radionuclide angiography and 201Tl scintigraphy (the latter in larger patient populations) have also demonstrated significant prognostic value on patients with or without previous myocardial infarction. Neither one has shown superiority to the other in prognostication. So far, they have been considered the only viable alternatives to exercise electrocardiography stress testing for diagnosis and prognostication. However, their costs limit their extensive application. Preliminary data suggest that intravenous dipyridamole echocardiography can be used for both diagnosis and prognostication of coronary artery disease; moreover, the prognostic information derived from dipyridamole echocardiography testing seems independent of and additive to that provided by exercise electrocardiography. Further prospective studies on larger patient populations are needed to better define the prognostic value of dipyridamole echocardiography testing.

Incidence and mechanisms of psychological stress-induced myocardial ischemia were investigated in a population of 63 patients using mental arithmetic. Fifty subjects (group 1) were selected as a consecutive population of ischemic patients with electrocardiographic documentation of ischemia at rest, on effort, or both. Mental arithmetic induced increases in heart rate, blood pressure, and rate-pressure product in all patients. Transient ischemic electrocardiographic changes occurred in 22 patients (44%; positive mental arithmetic), the majority of whom had both resting and exercise angina. In negative mental arithmetic tests, peak rate-pressure product was always lower than that achieved during exercise (mean +/- SD, 11.9 +/- 3 versus 21.3 +/- 5, p less than 0.01). Of the 22 patients with positive mental arithmetic tests, ischemia occurred in only six, at a rate-pressure product equal to or more than the one achieved during exercise (21.1 +/- 5 versus 19.4 +/- 4, p less than 0.01), suggesting an increase in myocardial O2 demand exceeding the limited increase in flow; in the remaining 16 patients, rate-pressure product values were significantly lower (14.8 +/- 3 versus 22.7 +/- 6, p less than 0.01), suggesting a primary reduction in coronary blood flow that is probably related to an increase in coronary tone. To assess the possible site of such a vasoconstriction, the effect of mental arithmetic on large coronary artery diameter was tested in 13 additional unselected patients (group 2) undergoing coronary angiography for a chest pain syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

The monitoring of aortic blood flow velocities by transcutaneous continuous-wave Doppler was performed in 45 patients to determine, non-invasively, the haemodynamic response to exercise in subsets of coronary patients during a multistage supine exercise tests. Group I consisted of 14 patients with ischaemia on effort (IE); group II, 12 patients with both IE and prior myocardial infarction (MI); group III, 19 patients with MI and no IE; there were also 12 normals. Peak flow velocity (PV) indices of cardiac output (CO), of peripheral resistance (PR) and of stroke work (SW) were measured every min. Resting CO was lower and PR higher in coronary patients than in normals. With exercise, for the same muscular work, CO increased less in IE patients (group I: y = 26.9 + 1.8 x cm sec-1; Group II: y = 21.9 + 1.8 x cm sec-1) than in MI (group III: y = 26.6 + 2.1 x cm s-1) and in normals (y = 35 + 2.7 x cm s-1) and PR decreased less. This suggested a more efficient distribution of CO towards working muscles. A shallower increase in SW was observed in all coronary patients in comparison with normals even if resting SW was significantly lower only in patients with MI (groups II and III). PV increased up to peak exercise only in group III, while it tended to plateau in ischaemic patients even earlier than IE occurred on the ECG.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the biocompatibility of four different types of oxygenator (bubble, membrane, hollow fibre and 'hybrid') was performed on 26 patients undergoing cardiopulmonary bypass during elective coronary surgery. More platelet derangement and an increased degree of hemolysis, revealed by higher plasmatic concentration of beta-thromboglobulin, platelet factor 4 and plasmatic free hemoglobin (p less than 0.05), was seen when using the bubble oxygenator. Damage to blood cells was minimal with the membrane oxygenator while the 'hybrid' and the hollow fibre oxygenators proved to rank at an intermediate level. Complement activation at the beginning of the cardiopulmonary bypass occurred via the alternative pathway as demonstrated by C3ades arg increase (up to nine times) without a concomitant elevation of C4ades arg. Cardiopulmonary bypass complement activation was quantitatively similar with all the oxygenators. A further activation via the classical pathway occurred in all the patients after protamine injection. Consistent differences as far as clinical and biological effects exist among the various commercially available cardiopulmonary bypass apparatus; our study provides guidelines for the evaluation and selection of devices which might reduce postoperative sequelae.

The effects of single-vessel coronary occlusion on simultaneously evaluated right (RV) and left ventricular (LV) performance were assessed and compared with LV perfusion patterns in 25 patients with variant angina. Coronary spasm involved the right coronary artery in 15 patients (group 1) and the left anterior descending coronary artery in 10 patients (group 2). Biventricular function was assessed by radionuclide angiography under basal conditions, during spontaneous or ergonovine-induced ischemia, and after resolution of the ischemic attack. Myocardial perfusion was assessed by thallium 201 scintigraphy in 21 patients of this series during superimposable ischemic episodes. In group 1, ischemia caused RV (14 of 15 patients) and LV (13 of 15 patients) regional dysfunction with significant reduction in RV and LV ejection fractions. The interventricular spetum was involved in six of 15 patients, causing a more pronounced LV impairment. In group 2, all patients showed septal dyssynergies associated with a reduction of LV ejection fraction; absent or trivial RV involvement was observed. In both groups, LV perfusion defects were present in all patients with LV wall motion abnormalities during ischemia, matching the site of regional dyssynergies. Thus, in a group of patients with variant angina and single-vessel disease, transient occlusion of the right coronary artery directly caused RV and LV impairment; in these patients, the extent of LV but not RV dysfunction appeared related to the presence of septal ischemia. Vasospasm of the left anterior descending coronary artery consistently caused LV dysfunction not associated with secondary effects on RV systolic function.

In 10 patients with frequent anginal attacks admitted to CCU, 2-lead ECG Holter monitoring (H-M) was performed for a total of 10 days. The number of ischemic episodes detected by retrospective analysis of H-M was compared with the number detected on the basis of symptoms and continuous visual ECG monitoring in CCU (CCU-M) by highly trained staff. A total of 157 episodes was identified by H-M [82 ST elevation (ST), 15 ST depression (ST) and 60 t wave changes]. Only 15 of these episodes were detected by CCU-M (13 ST, 1 ST and 1 T wave changes) of which 12 were symptomatic. When 6 H-M ECGs were simultaneously displayed on an oscilloscope in real-time (as in CCU-M), one of the Authors was able to detect only 36% of the episodes, whereas the frequency reached 80% when the analysis was limited to one tape at the time. The results show the low reliability of the CCU-M in detecting ischemic attacks; this appears mainly related to the display of multiple tracings.

The effects of oral verapamil (V), 400 mg/day, oral propranolol (P), 300 mg/day, and placebo were compared in 10 patients admitted to the coronary care unit because of frequent attacks of angina at rest. Testing was done according to a randomized, double-blind, multiple-crossover, placebo-controlled trial, consisting of 8 consecutive 48-hour treatment periods with V or P or placebo. Three patients had variant angina, 5 had episodes of both ST-segment elevation and depression and 2 had only ST-segment depression. One patient had no critical coronary stenoses, 1 had 1-vessel disease, 7 had 2-vessel disease and 1 had 3-vessel disease. Electrocardiographic monitoring and tape recording were continued during the 16 days of the trial. A total of 1,602 episodes of transient diagnostic ST shift were recorded during the trial (1,309 episodes of ST-segment elevation, 293 of ST-segment depression); 43% were painless. Mean blood levels of V and P at the end of the active phases were 161 +/- 89 and 120 +/- 45 ng/ml, respectively. In the group as a whole, the average number of diagnostic ischemic ST-segment shifts per 24 hours was significantly reduced relative to corresponding placebo periods during V (2.6 +/- 2.4 vs 11.9 +/- 8.6; p less than 0.01) but not during P treatment (11.9 +/- 8.6 vs 12.0 +/- 7.3). Similar statistically significant reductions were observed in the number of anginal attacks and nitroglycerin tablets consumed. Considering individual patients, V reduced ischemic episodes during both active phases in all patients, whereas P was effective only in 1.(ABSTRACT TRUNCATED AT 250 WORDS)

While the use of the 24 hour Holter monitoring for the detection of the cardiac arrhythmias and conduction disturbances is well established, its applicability to the monitoring of the ST segment and T wave for the detection of myocardial ischemia is controversial. For these reasons the Holter monitoring is mainly confined to the detection of cadiac arrhythmias and is used in those centers where computer facilities are available. We proposed to record the electrocardiographic tape replayed at 60 times the real time on a direct recording ultraviolet oscillograph running at low speed obtaining a fast compact analogue representation of the Holter recording where the 24 hour Holter recording is compressed into cm 480 of paper. The analogue compact representation described allows an easy detection of the transient displacement of the ST segment and/or changes in the T wave amplitude and direction and/or QRS pattern all due to myocardial ischemia without the use of any expensive computer facilities.

Cardiac pain is a key symptom for diagnosis of myocardial ischemia in man, even if a minority of transient myocardial ischemic episodes are painful. A multiparametric monitoring approach - associating non-invasive and invasive monitoring techniques during transient myocardial ischemia with and without pain - allows to achieve a clinical diagnosis and obtain information about the pathophysiology of the anginal syndrome.

This study assessed both group and individual variability of ECG exercise stress test in patients with effort angina. Forty-five untreated patients with typical effort angina, without evidence of spontaneous angina, with a positive exercise stress test (ST depression greater than 0.2 mV) and angiographically documented coronary artery disease were studied. Four multistage exercise stress tests were performed, two in the morning and two in the afternoon, on two consecutive days. Forty-four patients completed the protocol for a total of 176 exercise stress tests. For each exercise stress test the following parameters were analyzed: time to 0.15 mV ST segment depression (time to ischemia); rate-pressure product at ischemia (ischemic threshold); slope and intercept of the linear regression between rate-pressure product and time of exercise. Silent effort ischemia was largely prevalent: 21 patients (48%) experienced chest pain in all four tests, but only seven showed a consistent time relationship between pain and ECG changes. Symptomatic patients did not appear different from the asymptomatic ones in terms of clinical and angiographic data. When group data were analyzed for each parameter the four exercise stress tests appeared reproducible. In contrast, when individual variability of each parameter was computed as the percentage difference between range (maximum--minimum) and maximal value obtained in the series of four exercise stress tests, a large variability was detected. Variability of time to ischemia, was 27.2 +/- 17.4%. This resulted from a random combination of variability in ischemic threshold (19.1 +/- 9.2%), slope (28.4 +/- 12.8%) and intercept (22.7 +/- 10%).(ABSTRACT TRUNCATED AT 250 WORDS)

We evaluated the long-term therapy with Isosorbide Dinitrate Ointment (ISDN-O): 300 mg daily on the painful leg area in 20 male patients (pts) affected by Intermittent Claudication. The efficacy of the treatment was assessed on the basis of the subjective evaluation of pain threshold (daily diary) and objectively by repeated treadmill stress tests performed by each patient at a constant speed, selected according to the severity of symptoms, and by the evaluation of changes both of the distance walked without symptoms (DWS) and of the maximal distance reached (MDR). The maximal duration of the test was 15 minutes independently from the speed. The reproducibility of treadmill tests and the acute effect of isosorbide dinitrate ointment administration were preliminarly evaluated in 2 groups of 5 patients each. The distance walked without symptoms and maximal distance reached in two control stress tests performed in two successive days were: distance walked without symptoms 37 +/- 29 vs 36 +/- 22 m (NS) and maximal distance reached 97 +/- 40 vs 98 +/- 37 m (NS). During the control period and 1 hour after the drug administration distance walked without symptoms was 34 +/- 31 vs 43 +/- 50 m (NS) and maximal distance reached 89 +/- 53 vs 97 +/- 57, (NS) respectively. In a group of 5 patients the effect of one month administration of placebo was evaluated: distance walked without symptoms was m 68 +/- 29 and m 104 +/- 62 and maximal distance reached was m 156 +/- 103 and m 188 +/- 97 basally and after 1 month of placebo (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

M-mode echocardiograms were recorded in 12 patients with Prinzmetal's angina during 29 episodes of transient myocardial ischemia at rest (18 spontaneous and 11 ergonovine-induced). At peak ST segment elevation a regional mechanical impairment was observed in the interventricular septum during 23 episodes of angina and in the posterior wall during six episodes. In the 18 spontaneous episodes the left ventricular ischemic wall, when compared to the basal state, was found to have a significant reduction in motion (-76.3 +/- 9.1%) (mean +/- SEM), in diastolic thickness (-11.7 +/- 2.5%), and in percent systolic thickening (-88.0 +/- 5.6%). Increase in left ventricular end-diastolic diameter (+13.1 +/- 2.1%) and decrease in percent fractional shortening (-38.1 +/- 3.7%) were also observed. When ST segment was back to the isoelectric line, a transient overshoot in regional left ventricular function was observed. In induced episodes statistically significant changes could be detected by M-mode echocardiography even before appearance of ST segment elevation and anginal pain. No significant difference was found in type or degree of mechanical impairment between induced and spontaneous episodes. Therefore, in patients with Prinzmetal's angina: (1) M-mode echocardiography allows detection of mechanical changes due to transient myocardial ischemia; and (2) mechanical impairment occurs earlier than clinical (pain) and electrocardiographic (ST segment elevation) signs of transmural ischemia.

Visual monitoring at the central station of coronary care units (CCUs) may not adequately assess the presence and frequency of transient asymptomatic ST segment changes in patients with unstable angina. We have performed continuous 24-h electrocardiographic recordings over a total period of 50 days in 10 patients admitted to our CCU with frequent attacks of angina at rest. Over the corresponding period, at the central monitoring station (6 beds), the nursing-staff detected only 31 transient ischaemic episodes (27 with ST elevation, 4 with depression, 9 of which were asymptomatic). By contrast the retrospective analogue analysis of tapes identified 213 ischaemic episodes: 143 with ST elevation (greater than or equal to 0.2 mV) and 70 with ST depression (greater than or equal to 0.2 mV); usual CCU monitoring failed to report changes during 13 episodes (8 with ST elevation, 5 with depression) accompanied by anginal pain. When the tapes were played back in real time on a CCU monitoring scope, a cardiologist (who had the option of interrupting the play-back whenever tired) recognized 48% of the episodes when presented in groups of 4 and randomly positioned on the screen together with 2 other electrocardiographic tracings not related to the study; he recognized 92% of the episodes when only one ECG was presented on the screen. Thus conventional visual monitoring in a CCU considerably underestimates the incidence of transient ischaemic ST segment changes, some of which were accompanied by pain. This low rate of detection is the result of the presentation on the central monitoring station of several ECGs and of fatigue.

The purpose of this study was to evaluate the prognostic usefulness of basal electrocardiogram and exercise stress test in 374 patients with unstable angina submitted to coronary angiography during the same hospitalization period. After stabilization of symptoms by medical therapy, patients were subdivided into four groups according to the ECG and stress test: Group 1 (54 patients with normal ECG and exercise stress test negative for ischaemia); Group 2 (86 patients with normal ECG and exercise stress test positive for ischaemia); Group 3 (59 patients with abnormal ECG and exercise stress test negative for ischaemia); Group 4 (175 patients with abnormal ECG and exercise stress test positive for ischaemia). The severity of coronary atherosclerosis and impairment of left ventricular function increased progressively from Group 1 to 4, although differences in ventricular function were not significant between Groups 2 and 3. When discharged, patients were treated with verapamil and nitrates and followed for a period ranging from 1 to 8 years; during follow-up, only one patient of Group 1 underwent coronary bypass surgery, compared to 22, 7 and 46 patients in Groups 2, 3 and 4, respectively. The eight-year survival rate in the four groups (1-4) was 100%, 97%, 88% and 70%, respectively. Statistically significant differences were observed between Groups 1 and 3, 1 and 4, 2 and 4, and 3 and 4. Thus, the ECG and exercise stress test allow a population of patients with unstable angina to be selected (Group 1), having excellent long-term prognosis. These patients could avoid angiography, thereby reducing hospital costs, without compromising their health.

We studied regional myocardial perfusion by scintigraphic computer-assisted analysis of initial distribution, washout rates, and residual activity of 133Xe injected into the left coronary artery of four patients with normal arteriograms and 14 patients with coronary stenosis. At rest, residual activity in poststenotic regions was always greater than in control regions, but initial washout rates were not slower. During angina, following xenon injections, the amount of indicator distributed to the poststenotic regions was markedly reduced; the increase of the initial washout rates was smaller than in control regions relative to rest, and residual activity was higher. Initial washout rates did not differ as much as from those of normal myocardium because in severe ischemia too little indicator is deposited initially in these regions to produce a change of any magnitude. Indeed, when angina was induced immediately after the xenon injection, poststenotic washout rates became much slower during angina than at rest, a finding that implicates functional factors in impairing poststenotic myocardial perfusion during angina.

The effect of various doses of intracoronary verapamil on the diameter of angiographically normal left coronary artery segments was investigated in 22 patients with and without coronary atherosclerosis by quantitative angiography. Very low doses (50 micrograms) were given in 3 patients; doses of 250 micrograms, 350 micrograms and 500 micrograms were administered in 7, 6 and 13 patients, respectively. A single dose was administered in 15 patients, while two increasing doses of verapamil were tested in 7. The effect of verapamil was compared in each patient with that of nitroglycerin (NG; 0.6 mg), administered sublingually in all as the last step of the study. An additional group of 8 patients served as the control. These patients received 4 intracoronary injections of contrast medium without drugs and a fifth injection following 0.6 mg of sublingual NG. In the control group no significant changes in coronary artery diameter were observed following the four control injections of contrast medium, while a 18 +/- 9% increase in vascular diameter was observed following NG. When verapamil was injected a dose-dependent vasodilation was observed, which began to be significant with doses higher than 250 micrograms. Mean percent variations of coronary artery diameter relative to control were -0.2 +/- 3.6%, 4.6 +/- 5.5%, 11.4 +/- 7.5% and 19.9 +/- 10.7%, in response to verapamil doses of 50, 250, 350 and 500 micrograms, respectively. Subsequent nitroglycerin induced a 21.5 +/- 10.7% mean percent coronary artery dilation (NS vs verapamil 500 micrograms and vs NG in the control group). Thus, verapamil induced a dose-dependent coronary vasodilation which at a dose of 500 micrograms was comparable to that induced by NG. Both with verapamil and NG the smallest vessels exhibited the greatest vasodilation. It is concluded that at the doses used in this study, injection of verapamil into the left coronary artery is safe and markedly decreases tone in the large coronary arteries. This finding supports the use of verapamil in clinical conditions in which the role of coronary vasoconstriction is proven or thought to be relevant.

Eleven patients with frequent episodes of variant angina underwent 24-hour electrocardiographic monitoring in a coronary care unit for a total of 70 days to assess circadian variation in ischemic episodes and its correlation with circadian heart rate (HR) rhythm. In each patient a series of 4 to 13 consecutive days, in the absence of therapy, with 8 or more ischemic episodes per day were analyzed. Harmonic regression models were fitted to the hourly number of ischemic episodes and the hourly values of HR. Out of 54 days, with 8 or more episodes per day for a total of 1,357 episodes, a circadian rhythm was observed for 34 days (64%), in at least 1 day in all patients and during the entire period of observation in only 3. Its presence was independent of the number of episodes; the peak of periodic functions occurred at 2.9 +/- 2.7 AM. A cadian rhythm for HR was observed in 61 of the 70 days (87%), consistently in 7 patients; the nadir occurred at 2.4 +/- 1.5 AM; simultaneous cycling in HR and transient ischemia was found on 32 days. The intrapatient difference between the peak and the nadir of the ischemic and the HR function was, on average, 2.6 +/- 3.3 hours. Thus, a circadian rhythm of ischemic episodes was present in all patients although it was not consistently present; simultaneous occurrence of circadian variation in ischemic episodes and HR was observed only in 60% of the days with a sufficiently high number of attacks and when this occurred, a significant phase shift was observed; occasional loss of HR cycling was observed in some patients, without an apparent cause.

In the diagnosis of ischemic heart disease, long-term ECG recording has several distinct advantages. It allows one to relate patient symptoms to cardiac disturbances and to detect asymptomatic events, reveals the possible ischemic genesis of arrhythmias, and it is the most suitable method to assess the acute and chronic effectiveness of treatment and the evolution of the disease. In spite of these advantages, Holter monitoring has several limitations: the analysis of a single lead, is responsible in most systems for the low sensitivity in detecting ischemia occurring in unexplored regions; the period of 24-48 hours may not be sufficient for screening patients due to the unpredictable spontaneous variability of the disease; a common standard of analysis is still lacking even if the European Communities concerted action in Ambulatory Monitoring could represent the solution to this problem. Nevertheless the role of Holter monitoring appears essential in the ambulatory screening of patients with suspected ischemia for a better characterization of patients with ascertained myocardial ischemia, and for the evaluation of treatment and of the evolution of the disease.

In the diagnosis of ischemic heart disease, long-term electrocardiographic recording has several distinct advantages. It allows one to relate patient symptoms to cardiac disturbances and to detect asymptomatic events, furnishes the whole spectrum of electrocardiographic alterations accompanying ischemic attacks, reveals the possible ischemic genesis of dysrhythmias, and is the most suitable method to assess the acute and chronic effectiveness of treatment and the evolution of the disease. In addition to its valuable application in the screening and follow-up of ambulatory patients, its use in the Coronary Care Unit is of great interest, being in this context much more sensitive than visual electrocardiographic monitoring. In spite of these advantages, Holter monitoring has several limitations: the recording and replay systems are below recommended standards; the analysis of a single lead is responsible in most systems for the low sensitivity in detecting ischemia occurring in unexplored regions; the period of 24-48 hours, usually adopted for Holter monitoring, may not be sufficient for screening patients with suspected myocardial ischemia due to the unpredictable spontaneous variability of the disease; a common standard of analysis is still lacking and a reliable computerized analysis is needed to manage data overflow. In conclusion, although further research and technical developments are desired to improve reliability and data processing, the role of Holter monitoring appears essential in the ambulatory screening of patients with suspected ischemia for a better characterization of patients with ascertained myocardial ischemia, and for the evaluation of treatment and of the evolution of the disease.

Platelet function (aggregation by ADP, adrenaline, collagen and circulating platelet aggregates) before, during and after dietary induction of hyperuricemia (ribonucleic acid, 3 g/day) was studied in five healthy volunteers to assess the relationship between uric acid level and platelet function. In the same subjects, during a second period of ribonucleic acid diet, the acute and chronic effects of a hypo-uricemizing agent, allopurinol, were assessed. No significant correlation was detected between platelet function and uricemia either in the absence or in the presence of pharmacological treatment with allopurinol. On the basis of these results, the well known relationship between uric acid levels and ischemic heart disease does not appear to be mediated by an exaggerated platelet function.

From January 1970 to June 1985, transient electrocardiographic changes at rest were documented in 652 patients admitted to our coronary care unit. Patients were stratified according to the type of electrocardiographic alteration at rest: 295 had ST-segment elevation (group 1), 106 T-wave changes (group 2) and 251 ST-segment depression (group 3). Patients in group 3, compared with groups 1 and 2, were more likely to have symptoms of coronary artery disease dating back many years (p less than 0.01 and p less than 0.01, respectively), a previous myocardial infarction (p less than 0.05 and difference not significant), a positive exercise test (p less than 0.01 and p less than 0.01), transient ST-T changes occurring in a higher number of electrocardiographic leads (p less than 0.01 and p less than 0.01), multivessel disease (p less than 0.001 and p less than 0.01) and poor ventricular function (p less than 0.01 and p less than 0.05). Despite these differences, the occurrence of acute myocardial infarction and cardiac death during hospitalization was much more frequent in group 1 compared with groups 2 (p less than 0.02) and 3 (p less than 0.05). However, death occurred in those patients who had poor ventricular function and severe atherosclerosis. A greater susceptibility of group 1 patients to severe vasoconstriction documented by the ergonovine test and by the occurrence of spontaneous spasm seems to account for different in-hospital outcome.

The cardiovascular effects of dilazep, a new antianginal drug, were investigated in 18 patients, who underwent cardiac catheterization and coronary angiography for the evaluation of chest pain. Dilazep, 0.2 mg/kg, was injected intravenously over 1 to 2 minutes. The changes induced by dilazep in coronary tone were assessed by quantitative angiography in four patients, changes in systemic and coronary hemodynamics and blood gases in eight patients, and changes in systemic and pulmonary hemodynamics and blood gases in six. In 6 of the 18 patients the effects on hemoglobin-O2 oxygen binding were also investigated. Following dilazep administration, we observed a marked reduction of coronary resistance (six patients) (0.5 vs 1.0 mm Hg X min X ml-1, p less than 0.01) and of aortic-coronary sinus oxygen difference (seven patients) (4.6 vs 12.3 vol%, p less than 0.01), and a 23% increase in coronary diameter (four patients) (p less than 0.001). Total systemic resistance was also reduced by dilazep (six patients). Conversely, only minimal or insignificant changes were observed in heart rate (14 patients), aortic pressure (14 patients), total pulmonary resistance (six patients), myocardial oxygen consumption (six patients), double product (14 patients), blood gases (seven patients), and hemoglobin-oxygen affinity (six patients). We conclude that dilazep exerts a powerful dilating action on coronary vasculature without appreciable increase of myocardial oxygen consumption and cardiac work simultaneously with a reduction of peripheral resistance.

Following the casual observation reported by one anginal patient of ours, of improvement of its claudicatio intermittens with application of isosorbide dinitrate ointment directly on the leg suffering pain, we undertook a study to assess the possible use of the drug in peripheral vascular disease in a group of 10 patients suffering of a severe form of claudicatio intermittens. The effect of the drug was tested 1) by the subjective valuation of the patient itself 2) by treadmill stress tests performed at constant rate. In this case were used as reference parameters the distance walked without any symptoms and the maximal distance reached by each patient. The treadmill stress test was performed in basal condition and after longterm administration of isosorbide dinitrate ointment 100 mg three times a day for 30-45 days. In 5 patients the control test was repeated twice in different days to evaluate the reproducibility of the measure that resulted good, while other 5 patients performed the test one hour following the application of the drug in order to assess a possible acute effect of the drug that was not present in any patient. All the patients noted an improvement in their walking capacity but only after 15-20 days of treatment. In basal condition the distance walked without any symptoms by the patients was on the average m. 51 (+/- 52) and the maximal distance reached was m. 143 (+/- 111), while after the treatment were m. 151 (+/- 136) and m. 384 (+/- 203) with a difference highly significative (p less than 0.05 and p less than 0.01 respectively). From our data although preliminary, it is apparent that longterm local application of isosorbide dinitrate is effective in the treatment of patients with peripheral vascular disease and that the action of the drug seems to be related to a local effect.

A retrospective study of 107 patients who sustained an acute myocardial infarction (AMI) during hospitalization was undertaken to assess the early prognosis of Q wave AMI (55 patients, group 1) and no-Q wave AMI (52 patients, group 2). Forty-one patients in group 1 and 31 in group 2 had documented ischaemia at rest in the period preceding AMI. The incidence of pre-infarction ischaemic attacks was similar in Q wave AMI compared with non-Q wave AMI (average daily incidence per patient 3.1 +/- 4.3 vs 3.0 +/- 4.3). A 'crescendo' pattern of pre-infarction angina was rarely observed in both groups. The incidence of post-infarction ischaemia (documented in 28 patients of group 1 and in 28 of group 2) was greater, but not significantly, in group 2 (average daily incidence per patient 1.0 +/- 2.6 vs 1.4 +/- 3.2). All patients with pre-infarction ischaemia sustained infarction in the same territory. AMI in group 1 was always symptomatic while 12 AMIs in group 2 were totally asymptomatic. Fifty patients from group 1 and 27 from group 2 were on therapy while AMI developed. Twenty-one patients from group 1 showed life threatening arrhythmias (ventricular tachycardia, ventricular fibrillation, third degree AV block or asystole) during AMI; of these, 14 did not survive the arrhythmias; they all had signs of left ventricular failure. Only one patient from group 2 had runs of ventricular tachycardia, unrelated to AMI but during pre- and post-infarction ischaemia. The overall mortality rate of Q wave AMI was 29% while no deaths occurred in the non-Q wave AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

The time course of the vasodilation of different segments of the epicardial coronary vasculature after three different doses of intracoronary isosorbide dinitrate (ISDN) was investigated in angiographically normal coronary arteries in 10 patients with quantitative coronary angiography. In five patients, 0.1 mg and 0.3 mg ISDN were injected intracoronary 30 minutes apart, and the effect of each dose was assessed at 1, 5, 10, and 15 minutes after the administration by serial angiograms. In five additional patients, a single dose of 3 mg was injected and coronary vasodilation was assessed at 1, 5, 10, 15, and 20 minutes. After each dose, dilation of epicardial coronary arteries occurred within 1 minute, peaked at 5 minutes and progressively decreased thereafter. Relative to control, peak percent diameter increase was (mean +/- SEM) 10% +/- 0.9% (p less than 0.01), 18.5% +/- 1.5% (p less than 0.01), and 26% +/- 2.1% (p less than 0.01) after 0.1, 0.3, and 3.0 mg, respectively. When small (1 to 2 mm), medium (2 to 3 mm), and large (greater than 3 mm) vessels were separately analyzed, peak response was respectively 12% +/- 1.3% (p less than 0.01), 9% +/- 1.9% (p less than 0.01), and 7% +/- 1% (p less than 0.05) after 0.1 mg ISDN; 22% +/- 1.8% (p less than 0.01), 16% +/- 1.3% (p less than 0.01), and 12% +/- 0.8% (p less than 0.01) after 0.3 mg; and 38% +/- 2.4% (p less than 0.01), 22% +/- 2.1% (p less than 0.01), and 17% +/- 2% (p less than 0.01) after 3.0 mg. The duration of the response increased with the dose, but was inversely related to the size of the vessel.(ABSTRACT TRUNCATED AT 250 WORDS)

We studied the value of dipyridamole-echocardiography test in comparison with clinical, resting electrocardiogram and echocardiogram variables in predicting cardiac events occurring in 539 consecutive patients referred for dipyridamole-echocardiography test from 1984 to 1987. There were 118 cardiac events: 11 cardiac deaths, 12 nonfatal myocardial infarctions, and 95 coronary revascularization (bypass or angioplasty) procedures. A Cox survival analysis identified echocardiographic positivity after dipyridamole administration as the best predictor of cardiac events (relative risk ratio, 2.7). The next most powerful predictor was angina after dipyridamole administration (relative risk ratio, 1.9). Cardiac events occurred in 14 (6%) of 253 patients with normal high-dose dipyridamole echocardiographic test results, in 21 (26%) of 82 patients with high-dose dipyridamole echocardiographic positivity (0.84 mg/kg during 10 minutes), and in 83 (41%) of 204 patients with low-dose dipyridamole echocardiographic positivity (0.56 mg/kg during 4 minutes) (p less than 0.0001). In a subset of 341 patients, exercise electrocardiography stress test and coronary angiography were also available. A Cox survival analysis again identified echocardiographic positivity after dipyridamole as the best predictor of cardiac events (relative risk ratio, 1.9) followed by a pathologic coronary arteriography (relative risk ratio, 1.2). We conclude that the presence and timing of a transient dyssynergy during dipyridamole stress are useful predictors of subsequent cardiac events.

The possible role of prostaglandins in mediating large coronary artery vasodilation by nitrates was investigated by quantitative magnification coronary angiography. The effects of aspirin (1 g systemically and 100 mg intracoronary) in preventing large coronary artery vasodilation induced by intracoronary isosorbide dinitrate was investigated in 16 patients. Of these, 5 received 0.3 mg (Group 1A) and 11 received 3 mg (Group 1B) intracoronary isosorbide dinitrate, before and 15 minutes after aspirin. Relative to control, 0.3 mg isosorbide dinitrate induced a 19 +/- 9% (mean +/- SD) (p less than 0.01) and 19.5 +/- 11% (p less than 0.01) increase in coronary diameter before and after aspirin, respectively (p = NS). Changes after 3 mg isosorbide were 23 +/- 12% (p less than 0.01) and 26.5 +/- 14% (p less than 0.01), respectively, before and after aspirin (p = NS). In 10 additional patients (Group 2), the effect of the same dose of aspirin on rest coronary artery tone was assessed: changes relative to control were 0.9 +/- 5.5% (p = NS) minutes after aspirin. The intracoronary administration of 3 mg isosorbide dinitrate produced a 24.7 +/- 11% increase in coronary diameter (p = NS versus pre- and postaspirin isosorbide in Group 1B). Urinary 6-ketoprostaglandin-F1 alpha values in urine samples collected in the 8 hours before and the 8 hours after the study in five patients in Group 1B and five patients of Group 2, revealed a 36 +/- 14% (mean +/- SD) reduction in excretion of prostacyclin (p less than 0.01). These data rule out a role for prostaglandins both in mediating dilation of large coronary arteries by nitrates and in affecting their vascular tone at rest.

A medical approach to treatment was adopted in 652 patients with documented myocardial ischemia at rest during both the acute and follow-up phases. No patient underwent coronary revascularization during hospitalization and only 86 patients (13%) underwent coronary bypass surgery within 8 months from discharge. During hospitalization 13 patients died. In the remaining group (639 patients), the likelihood of death in the 10-year period after discharge was 28% for all patients and 20% for cardiac causes only. A series of factors studied during the acute stage were assessed in an effort to predict long-term outcome. The following noninvasive characteristics, listed in decreasing order of statistical significance, were found to be significant univariate predictors of survival: abnormal basal electrocardiogram, duration of coronary artery disease, previous myocardial infarction, pattern of ST-T changes during episodes of ischemia at rest, age and systemic hypertension. The average annual mortality rate for patients with T-wave changes, ST-segment elevation and ST-segment depression was 0.9, 1.8 and 3%, respectively. The Cox survival analysis identified abnormal basal electrocardiogram, duration of coronary artery disease and pattern of ST-T changes as significant, independent predictors of death. When invasive characteristics were entered in the model, number of greater than or equal to 50% narrowed coronary arteries, left ventricular ejection fraction, abnormal basal electrocardiogram and smoking habit were found to be independent and additive prognostic variables. Thus, long-term prognosis of patients with ischemia at rest is related to the severity of anatomic impairment, independent of the pattern of ST-T changes observed during the acute phase.(ABSTRACT TRUNCATED AT 250 WORDS)

This study explores the effects on some hematological parameters of a low-dose aspirin regimen (50 mg/day) versus a conventional aspirin treatment with reported antithrombotic efficacy (324 mg/day), in patients with acute myocardial infarction. Fifteen patients were randomized into 3 equal groups receiving 50 mg or 324 mg aspirin or placebo, daily for 21 days. Compared with placebo, bleeding time was significantly and similarly prolonged with both aspirin doses (+ 71 +/- 22% and + 69 +/- 20%, mean +/- S.D.). Aspirin 50 mg/day suppressed arachidonate-induced platelet aggregation and secondary phase aggregation after ADP and adrenaline. Collagen aggregation was inhibited by 44 +/- 15%. In no case were differences in the antiplatelet effects of the two doses observed. The effects of 50 mg/day persisted without attenuation during the observation period. Platelet thromboxane B2 generation during arachidonate-induced aggregation was inhibited by 95 +/- 2 and 99 +/- 1% compared to placebo group after 50 and 324 mg/day, respectively (P between doses less than 0.05). No change was observed with any treatment in coagulation time, prothrombin time or plasma thromboplastin time. Thus, in patients with acute myocardial infarction, the antiplatelet effects of aspirin 50 mg/day are stable over time and superimposable on those of 324 mg/day. The antithrombotic efficacy of aspirin 50 mg/day remains to be tested clinically.

Asymptomatic episodes of ST segment and/or T wave changes are often reported during Holter monitoring in patients with angina pectoris. However, the interpretation of such changes is debated relative to silent myocardial ischemia. We studied 11 patients admitted to the CCU because of frequent episodes of unstable anginal attacks who had undergone repeated periods of Holter monitoring, characterized by predominantly occurring asymptomatic episodes of ST segment and/or T wave changes associated with less frequent typical anginal attacks. In a total of 89 days of Holter monitoring, the patients evidenced 520 episodes of transient ECG changes including 180 of ST elevation, 73 of ST depression, and 267 of T wave alterations. Only 12% of episodes were symptomatic. Coronary injection during asymptomatic ST-T changes was performed in eight patients. In six it was possible to document spontaneous coronary spasm. In seven patients ergonovine administration induced anginal pain, ST-T changes, and coronary spasm. In all patients the anginal attacks completely disappeared with medical treatment and the asymptomatic episodes were abolished in six and reduced in four. Our findings support the hypothesis that in certain selected unstable anginal patients, transient asymptomatic ECG changes are caused by acute myocardial ischemia.

Twenty-four patients with effort angina and positive exercise stress test performed four control exercise stress tests, two tests while taking propranolol (240 mg/day) and two tests while taking verapamil (320 mg/day), in a randomized crossover sequence. For each test the following parameters were measured: time and rate-pressure product at ischemia; intercept and slope of the linear regression between rate-pressure product and minutes of exercise. Group analysis showed that both drugs improved time to ischemia significantly and to the same extent. However, eight patients responded preferentially to verapamil in contrast to 12 patients on propranolol. The remaining four patients responded equally to both drugs. In verapamil responders, verapamil increased time to ischemia by decreasing intercept and increasing rate-pressure product at ischemia. In these patients, propranolol did not increase time to ischemia because of a marked decrease in rate-pressure product at ischemia. In propranolol responders the significant increase in time to ischemia during propranolol was the result of a decrease in intercept and slope. The ineffectiveness of verapamil in these patients was related to a slight decrease in intercept without any increase in rate-pressure product at ischemia. The preferential response to one of the two drugs could not be predicted on the basis of clinical and angiographic features. In conclusion, in patients with effort angina, medical treatment should be personalized and based on a direct and objective verification of a drug's efficacy since different mechanisms can modulate exercise tolerance.

In patients with ischemic heart disease the evaluation of regional myocardial perfusion by 133Xenon intracoronary injection using a gamma camera computer system allows the detection of regional alterations of myocardial perfusion. While at rest a minority of the patients studied shows large alterations, during pacing induced angina a severe reduction of regional myocardial perfusion can be evidenced both in initial distribution scintigrams, when the injection is performed during angina, and on the washout curves when angina is induced immediately after the injection, during the course of the washout.

Nitrendipine is a second-generation dihydropyridine calcium antagonist selective for hypertension. The aim of this study was to assess whether, in addition to reduce resting blood pressure, nitrendipine also affects the cardiovascular reactivity to physical and psychologic stress. Ten essential hypertensive patients, out of treatment for at least 2 weeks, underwent a symptom-limited dynamic maximal exercise and a mental arithmetic stress test (MAT) after placebo (1 week) and 1 and 5 weeks of active treatment with nitrendipine (20 mg q.i.d.). To evaluate the cardiovascular response to exercise and its changes during treatment, the slope of the regression line (if statistically significant) of the blood pressure, heart rate, and rate-pressure product (RPP) values against workload were considered, together with exercise capacity, blood pressure, and pressure-rate product at the peak of maximal exercise. During mental stress, indexes of stroke volume (SVI), cardiac output (COI), and peripheral resistance (TPRI) were obtained by Doppler transcutaneous aortovelography (TAV). Resting systolic and diastolic BP were significantly reduced during treatment. The average length of exercise was 7.3, 7.64, and 8.0 min after, respectively, placebo, 1, and 5 weeks of treatment. Peak systolic and diastolic BP, peak RPP, and RPP slope were consistently decreased after treatment, significantly for peak DBP and RPP. During mental arithmetics, a significant increase of BP and HR and a decrease of SVI were observed on placebo; both BP and SVI responses disappeared after 5 weeks on nitrendipine, whereas the HR increase was unchanged. Peak values of COI and TPRI during MAT were significantly increased and decreased, respectively, after nitrendipine, whereas basal values showed similar changes, but not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)