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The clinical significance of repetitive ventricular complexes (RVCs) during pre-discharge bicycle ergometry after acute myocardial infarction has been assessed in 408 consecutive patients. RVCs occurred in 32 patients (8%). When compared to patients without RVCs, those with RVCs had a larger infarction, a higher prevalence of heart failure and late sustained ventricular tachycardia or fibrillation, a lower radionuclide ejection fraction and more frequent RVCs during pre-discharge 24-hour electrocardiographic monitoring. During a follow-up 30 patients died, 17 suddenly. Mortality was 15% (N = 5) in patients with RVCs during exercise test and 7% (N = 25) in those without RVCs. Sudden death occurred in only one patient with RVCs. When multivariate analysis was applied to clinical and exercise test data, RVCs during exercise did not predict cardiac mortality independent of variables related to left ventricular function, such as a history of previous myocardial infarction, persistence of heart failure in the late hospital phase and the extent of blood pressure rise during exercise test.

This study is a retrospective analysis of the efficacy of percutaneous transluminal coronary angioplasty of the ischaemia-related vessel in patients with unstable angina. Forty-three patients had multivessel disease with dilatation of the ischaemia-related vessel only (group I; partial revascularization) while 111 patients had single vessel disease only (group II; total revascularization). The initial success rate in both groups was identical (88 versus 88%). The need for emergency coronary artery bypass surgery was similar in the two groups (group I 12% versus group II 9%; NS). The total post PTCA myocardial infarction rate (despite urgent CABG) was also similar in the two groups (group I 9% versus group II 10%; NS). The results of electrocardiographic exercise testing and Thallium-201 scintigraphy provide objective evidence for incomplete revascularization in group I. The maximum workload achieved was lower, and the frequency of exercise induced angina, ST-segment depression and reversible perfusion defect was higher than in group II. Moreover, at 6 months follow-up the recurrence rate of angina pectoris rate was higher in group I than in group II (29% versus 16% P less than 0.05). It is concluded that dilatation of the ischaemia related vessel only in patients with unstable angina and multivessel disease is as effective in the management of the acute phase of unstable angina as is dilatation of the ischaemia related vessel in patients with single vessel disease. However, due to only partial revascularization the recurrence rate of angina pectoris is higher.

In a clinical trial we studied left ventricular performance at rest in 50 patients with unstable angina by radionuclide techniques. Thallium-201 scintigraphy was performed on admission in 38 patients and repeated after 48 hr in 32 patients. Also dynamic blood pool scintigraphy was performed in 37 patients on admission and in 45 patients after 48 hr. Of the 50 patients, 27 (54%) had no recurrent episodes of myocardial ischemia, but 23 (46%) patients showed recurrent ischemic episodes of whom 11 (22%) patients developed a myocardial infarction. The thallium-201 images showed perfusion defects in 27 (71%) of the 38 patients studied on admission and in 20 (63%) of the 32 patients studied at 48 hr. No relation between clinical outcome and presence or absence of defects was observed. Left ventricular ejection fraction was abnormal (less than 50%) in 19 (51%) of the 37 patients on admission and in 29 (64%) of the 45 patients studied at 48 hr. As with thallium-201, no relation could be established between clinical outcome and left ventricular ejection fraction. It is concluded that radionuclide techniques are useful to provide insight into the pathophysiological mechanism of unstable angina, but they are not helpful for the short-time assessment of clinical outcome.

Alinidine has been shown to reduce heart rate in experimental animals and in humans. However, in contrast with the beta blockers, this effect is not mediated through adrenergic receptors. The potential value of this drug was tested in eight patients with coronary artery disease and stable angina pectoris. During a one-week period of hospitalisation, exercise tests were done on four successive days after administration of placebo, 20, 40 and 60 mg alinidine, in a randomized double-blind sequence. On each day, exercise tests were performed on a bicycle ergometer with workload increments of 20 W/min until angina or fatigue. A dose-dependent reduction of heart rate and of the rate-pressure product was observed after alinidine. Rate-pressure products at peak exercise were 242 ± 42, 218 ± 29, 206 ± 33 and 197 ± 33 after placebo and ascending doses of alinidine, respectively. Exercise tolerance improved by a mean of 16 W, while the highest load which was achieved without symptoms improved by 26 W with 60 mg of alinidine. It is concluded that alinidine reduces myocardial oxygen consumption and improves exercise tolerance in patients with angina. Its ultimate clinical value should be further evaluated in larger groups of patients.

The risk of bleeding associated with intracoronary infusion of streptokinase in acute myocardial infarction was determined in a randomised controlled trial containing 302 patients under the age of 70. Intracoronary streptokinase infusion was given to 152 patients and 150 patients were treated conventionally. Bleeding was seen in 24 (16%) patients in the streptokinase group and in two of the conventionally treated patients. Bleeding was most common (28%) in patients over the age of 60 years. The groin was the site of bleeding in all patients except one. In the first 48 hours after admission the haematocrit in streptokinase treated patients with manifest bleeding fell by 0.07 (0.04) (mean (SD)). The fall in haematocrit in the streptokinase treated patients without manifest bleeding was 0.05 (0.04) and in the conventionally treated patients it fell by 0.03 (0.04). Sixty six units of packed cells were transfused in the streptokinase group (50 units to those who bled); the control group required only 17 units. There were no deaths due to bleeding. The occurrence of bleeding and the fall in haematocrit in the streptokinase group correlated with the occurrence of systemic fibrinolysis but not with the dose of streptokinase given. Thus, in about 15% of patients treatment with intracoronary streptokinase resulted in significant non-fatal bleeding from the femoral puncture site that required substantial transfusion support. Furthermore, there was a significant drop in haematocrit in patients without manifest bleeding. These results emphasise the need for more specific fibrinolytic agents.

Immediate results and follow-up are reported on 118 patients with a diagnosis of myocardial infarction who were included in studies on intracoronary thrombolysis at the Thoraxcenter. Pilot studies included 37 patients treated with streptokinase, nine with urokinase and six with nitroglycerine and nifedipine. First results of the present on-going randomized trial are described from 34 patients allocated to streptokinase therapy and 32 allocated to conventional therapy in the coronary care unit. Urokinase, nitroglycerine and nifedipine were not effective for recanalization. Streptokinase resulted in recanalization of 22 out of 29 occluded arteries in the pilot studies (71%), as well as 19 out of 23 occluded arteries in the randomized trial (83%). Five patients died during angiography and attempted recanalization. In the pilot studies, four patients died during follow-up. In none of these had recanalization been achieved. On the other hand, angina and reinfarction were observed more frequently in patients after successful recanalization. In the randomized trial no differences were observed in mortality, reinfarction rate, angina or results of predischarge stress testing between patients allocated to streptokinase treatment or controls. However, cardiac -failure during follow-up seemed to be more prominent in controls. These preliminary data indicate that the clinical course in patients after attempted thrombolysis is similar to the course of patients treated by conventional methods. Both should be monitored carefully for signs of cardiac failure and episodes of myocardial ischemia and appropriate measures, including surgery, should be considered if these appear. Further randomized trials are warranted to determine whether patients after thrombolytic therapy have a better survival and fewer complications than patients treated conventionally.

The effect of reperfusion achieved by early intracoronary streptokinase in acute myocardial infarction on left ventricular function was studied in 533 patients enrolled in a prospective randomised multicentre study. Two hundred and sixty four patients were allocated to conventional treatment and 269 patients to thrombolysis. At the end of the procedure patency of the infarct related vessel was achieved in 198 (85%) of 234 patients in whom coronary angiography was performed. The median interval from onset of symptoms till the angiographic documentation of patency was 200 minutes. Data were analysed according to the original treatment allocation. Global left ventricular ejection fraction was determined by radionuclide angiography in 418 patients within two days of admission, in 361 patients after two weeks, and in 307 patients after three months. Global left ventricular function remained unchanged throughout the observation period in the control group, whereas it improved during the first two weeks in patients allocated to thrombolytic treatment. Improved function in these patients persisted up to three months after the infarction. Global left ventricular ejection fraction was significantly better in the thrombolysis group than in the control group at two days, two weeks, and at three months. In patients with anterior myocardial infarction the left ventricular ejection fraction was 9% better than in the control group at two weeks and at three months. In the patients with inferior myocardial infarction differences between the two treatment groups were smaller because of photon attenuation within the body. Angiographic evidence suggested that the improvement in function seen after thrombolysis is indeed associated with the patency of the infarct related artery.

In a consecutive series of 146 kidney transplant recipients treated with cyclosporin A a strong correlation between matching for the HLA-A, HLA-B, and HLA-DR loci specificities and outcome of the grafts was observed in male recipients with non-O blood groups. Such a beneficial effect of matching was not found in female patients or male patients with blood group O. In these patients survival of the grafts at one year was good irrespective of the number of HLA-A, B, and DR mismatches. Also in 47 male heart transplant recipients immune responsiveness against mismatched HLA antigens was related to blood group. A significantly higher incidence of rejection episodes was observed in male patients with non-O blood groups (n = 32) than in those with blood group O (n = 15). Matching for HLA-DR reduced the number of acute rejection episodes in male patients with non-O blood. These findings may help explain the controversial reports about the importance of HLA matching in organ transplantation. Furthermore, as most candidates for heart transplantation are male and not of blood group O, the higher incidence of graft rejection in these patients underscores the need for an exchange strategy of donor hearts.

Immediate PTCA following thrombolysis with streptokinase was performed in 46 out of 533 patients enrolled in a multicentre randomized trial of early reperfusion in patients with acute myocardial infarction. Additional effects of PTCA in patients with a residual diameter stenosis in the infarct-related coronary artery of 70% or more after thrombolysis were compared with successful thrombolysis alone in a matched pair analysis. Thirty six pairs of patients were formed identical with respect to the infarct related coronary artery, presence or absence of previous myocardial infarction, total ST segment elevation on the ECG at admission to the trial, and delay between onset of symptoms and hospital admission. PTCA after thrombolysis did not lead to additional limitation of infarct size, nor to further preservation of left ventricular function. Infarction rate during the three-year follow-up was 14% after PTCA versus 30% after thrombolysis alone (P = 0.05). Similarly, patients had less angina or heart failure after PTCA, since on average 128 out of 156 weeks follow-up were symptom free, while this was only 102 weeks after thrombolysis alone (P = 0.03). Immediate PTCA after thrombolysis with intracoronary streptokinase seems to prevent recurrent ischemia and reinfarction. Further studies should address the proper indication and timing of PTCA after thrombolysis.

The current revolution in the treatment of acute myocardial infarction by means of thrombolytic therapy has as its underlying strategy three aims: early restoration of the blood flow in order to salvage jeopardized but still viable tissues; limitation of acute consequences of ischemic heart disease, such as infarct size, ventricular fibrillation, and pericardial effusion; and preservation, as far as possible, of ventricular function. It is also hoped that these three achievements will result in reduced short- as well as long-term mortality rates. The techniques employed in this overall strategy are still under investigation, and several leading pharmacological compounds vie for supremacy: streptokinase (SK) and its anisoylated form (APSAC), recombinant technique tissue type plasminogen activator (rt-PA), and urokinase (UK) with or without prourokinase (PUK). Other pharmacological agents, such as angiotensin converting enzyme (ACE) inhibitors, beta-blockers, Ca2+ antagonists, and O2 radical scavengers, might find here their "finest hour" yet. In addition, the underlying anatomy may require early or, where needed, delayed PTCA, backed up by coronary artery bypass grafting. Thus, the tactics of the intervention may vary from case to case and indeed from center to center depending on experience and facilities, but the strategic conclusion is clearly the same: early reperfusion is a must if one wishes to save ischemic but still viable tissue.

In 1981 we initiated a randomized trial at the Thoraxcenter in Rotterdam which was later extended to include four other hospitals cooperating in the Netherlands Interuniversity Cardiology Institute: the Zuiderziekenhuis in Rotterdam, the Free University in Amsterdam, the St. Annadal Hospital in Maastricht and the Leiden University Hospital. Since the global results of the study have been published in the Lancet (4) and in other journals (3, 5) we present a summary of the findings and discuss the clinical consequences of the trial.

Alinidine is a new sinus node inhibitor which does not interact with the beta adrenergic receptors. Its haemodynamic effects were studied in 57 patients; 24 with unstable angina, 9 with myocardial infarction and heart rate greater than 100 bpm but without heart failure. 10 with myocardial infarction treated with vasodilators and 14 with severe heart failure or shock. After dosages up to 40 mg alinidine, heart rate decreased by 14 +/- 7 bpm, mean arterial pressure was reduced by 3 +/- 6 mmHg, stroke volume remained unchanged while cardiac output decreased 0.5 +/- 0.61 min-1 and systemic vascular resistance increased. Signs of heart failure developed in 3 patients, although overall left ventricular filling pressure remained unchanged. The haemodynamic response to alinidine warrants further studies of its efficacy in patients with angina or sinus tachycardia.

From the literature which has appeared over the last decade a selection was made of the three major calcium antagonists: nifedipine, verapamil and diltiazem. In the clinical situation, the net hemodynamic and electrophysiological effect of these drugs is the result of complex interactions between their peripheral and their central effects. The degree of baroceptor stimulation and reflex mediated beta-adrenergic activity, which counteracts and influences the intrinsic negative dromotopic, chronotopic and inotropic effects of calcium antagonists, are related to the degree of peripheral dilation. Nifedipine is the most potent arterial vasodilator and is consequently associated with the most intense reflex adrenergenic activity. Although their effects on vascular and cardiac muscle are similar but not identical, there exist major differences in their antiarrhythmic properties. All act as an antiarrhythmic agent when ischemia or reperfusion cause the arrhythmias, while verapamil selectively blocks the A-V node conduction. All three discussed calcium antagonists are effective in treating patients with coronary spasm, variant angina and unstable angina. In our personal experience with 73 patients with unstable angina with prolonged severe pain at rest with transient ST-segments and T-wavechanges without elevated enzyme levels, 21 became asymptomatic within 8 hours of treatment with conventional therapy, which included nitrates and betablockers. Of 52 who remained refractory to such therapy, the addition of 10 mg of nifedipine orally every two hours to a maximum of 60 mg rendered 42 of the 52 asymptomatic within 8 hours. Arguments why we believe that the timely administration of nifedipine to these and similar patients will reduce or delay the incidence of arrhythmias and myocardial infarction are given on the basis of experimental data. Nifedipine greatly dilates coronary arteries, an effect which persists even after the drug's general hemodynamic effects disappear. It is shown that antagonists have anti-ischemic properties which are primarily related to the persistent reduction of the basic coronary vascular tone which increases oxygen supply whilst reduced myocardial contractility leads to decreased oxygen consumption. Furthermore, preservation of cellular integrity is achieved via protection against intracellular Ca2+ excess, as demonstrated by preserved intracellular high energy phosphate. A randomized multicenter trial in the Netherlands is now in progress to clarify the definitive role of beta blockade versus calcium antagonists therapy of their combination in this syndrome.

Intracoronary streptokinase was infused to 152 randomly selected patients after acute myocardial infarction (MI). Control group consisted of 150 randomly selected patients after MI who were treated by conventional methods. Preliminary results indicate several beneficial effects of early reperfusion with intracoronary streptokinase.

The diagnosis of stable coronary artery disease can be established by making a careful history of the patient, documentation of ECG changes during episodes of coronary insufficiency, visualization of regions with temporarily impaired uptake of thallium-201 or other isotopes, measurement of impaired left ventricular function during ischemic episodes and, finally, coronary arteriography. Optimal results will be obtained when the proper methods are selected for each individual patient.

It is dangerous to take a position on the “state of the art” of thrombolytic therapy, particularly since a number of larger studies are being conducted and may be completed before this paper appears. The available data at the time of this meeting have convinced us that thrombolytic therapy is the preferred mode of treatment in a subgroup of patients with acute myocardial infarction: patients with extensive anterior myocardial ischemia or inferoposterior ischemia, who can be treated within 4–6 h after the onset of symptoms.

The association of increasing serum levels of fibrinogen degradation products after recombinant tissue-type plasminogen activator (rt-PA) therapy with bleeding and early coronary patency was assessed in 242 patients with acute myocardial infarction. After administration of 5,000 IU heparin, a median of 40 mg (range 35 to 60) of double chain rt-PA was given intravenously in 90 min. Bleeding occurred in 62 patients; in 73% of patients it was observed within the 1st 24 h and 84% of events consisted of hematoma or prolonged bleeding, or both, at puncture sites. Bleeding events occurred 2.12 times as often in patients with serum levels of fibrinogen degradation products greater than 85 mg/liter as in patients with serum levels less than 22 mg/liter (95% confidence interval 1.01 to 4.43). The infarct-related coronary vessel was patent in 65% of patients at 90 min after the start of rt-PA infusion. In patients with high serum levels of fibrin(ogen) degradation products, coronary patency at 90 min after the start of rt-PA infusion was not better (13% less, 95% confidence interval - 33%, 13%) than in patients with low serum levels. This uncoupling of thrombolytic effect in terms of coronary patency and systemic fibrinogenolysis confirms the experimentally demonstrated fibrin specificity of double chain rt-PA in human subjects. Because fibrin specificity of single chain rt-PA is at least similar to that of double chain rt-PA, the observations in this analysis most likely hold also for single chain rt-PA.(ABSTRACT TRUNCATED AT 250 WORDS)

Restenosis of the dilated vessel after percutaneous transluminal coronary angioplasty can be detected by non-invasive procedures but their ability to predict later restenosis soon after a successful angioplasty as well as recurrence of angina has not been assessed. A maximal exercise test and myocardial thallium perfusion scintigraphy were, therefore, performed in 91 asymptomatic patients a median of 5 weeks after they had undergone a technically successful angioplasty. Primary success of the procedure was confirmed by the decrease in percentage diameter stenosis from 64(12)% to 30(13)% as measured from the coronary angiograms and in the trans-stenotic pressure gradient (normalised for mean aortic pressure) from 0.61(0.16) to 0.17(0.09). A clinical follow up examination (8.6(4.9) months later) was carried out in all patients and a late coronary angiogram obtained in 77. The thallium perfusion scintigram showing the presence or absence of a reversible defect was highly predictive for restenosis whereas the exercise test was not. The positive predictive value of an abnormal scintigram was 82% compared with 60% for the exercise test (ST segment depression/or angina or both at peak workload). Angina or a new myocardial infarction occurred in 60% of patients with abnormal and in 21% of patients with normal scintigrams.

Immediately after the first signs and symptoms of acute myocardial infarction are detected, its prognosis is determined by the size of the area at risk, the availability of collaterals and the time at which interventions are carried out. Preservation of as much myocardial tissue as possible is the key issue. Relief of obstruction of the thrombosed nutrient artery and reperfusion of the myocardium in jeopardy within 4 hours after onset of symptoms can lead to limitation of the ultimate infarct size, maintained ventricular function and a marked reduction of the first year mortality. Early supportive therapy with beta-blockade and calcium antagonists may enhance this effect. Recent data published on 533 patients randomized to either a reperfusion strategy or to conventional therapy, combined with those from the recent literature on thrombolysis and early beta blockade, provide the basis for this point of view. Once infarction is unavoidable and in the process of consolidation, supportive therapy is recommended. This still can change the outcome by timely correction of electrical instability, normalization of afterload and heart-rate, and the avoidance of secondary complications such as peripheral thrombosis. To determine the best course after recovery from the infarction, a symptom limited bicycle stress test, radionuclide ventriculography and 24 hour ambulatory electrocardiogram at the time of discharge were compared in predicting one year survival in 351 hospital survivors. A history of previous myocardial infarction or of heart failure during the current episode proved to be the strongest clinical predictor of early death.(ABSTRACT TRUNCATED AT 250 WORDS)

Recanalization in a developing myocardial infarction is a most worthy goal indeed inasmuch as it attempts to restore oxygen supply to the cardiac muscle deprived of its usual perfusion of oxygen rich blood when an intracoronary thrombus has formed. It also aims at restoring coronary vascular reserve to levels which can never be reached by drugtherapy. The very logic of this approach has allowed it so far to compete within the ever tightening budget of health expenditures. Nevertheless, comparisons as to its efficacy must be made in terms of its long-term effect, such as one year mortality and resteration of ventricular function, against other treatments which are considerably less expensive. It behooves the intelligent scientific researcher to consider such matters relatively early, at least just after the initial stage in proving the efficacy of new treatment has been established. It is quite clear that the case in favor of intracoronary streptokinase for some patients has now been made in that it has not only been shown that left ventricular function improves after successful recanalization, in the majority of patients, but also that there is a significant reduction in one year mortality in at least one subset of patients.

The effects of early intracoronary streptokinase (SK) on enzymatic infarct size and rate of enzyme release were studied in a randomized multicenter trial. A total of 533 patients with acute myocardial infarction (AMI) were allocated to either the SK treatment group (n = 269) or the conventional (control) treatment group (n = 264). Enzymatic infarct size was represented by the cumulative quantity of alpha-hydroxybutyrate dehydrogenase (HBDH) released by the heart per liter of plasma in the first 72 hours. Rate of enzyme release was represented by the ratio of HBDH quantities released in 24 hours and 72 hours. On an "intention to treat" basis, the SK group had a smaller (by 30%; p = 0.0001) median enzymatic infarct size and a higher (by 35%; p = 0.0001) median rate of enzyme release than the control group. Limitation of infarct size was less apparent in patients treated with intracoronary SK only (25%) than in patients treated with intravenous plus intracoronary SK (34%). Compared to the control group, the enzyme release rate in patients treated with intracoronary SK only was slightly less (34%) than that in patients treated with intravenous plus intracoronary SK (38%). Patients with a patent infarct-related coronary artery at acute angiography had a median infarct size which was 55% (p = 0.0001) smaller than the median infarct size of the control group, and the median rate of enzyme release was 38% (p = 0.001) higher than the median release rate of the control group. Patients with successful recanalization during intracoronary SK infusion had a median infarct size which was 31% (p = 0.002) smaller than the median infarct size of the control group and a median rate of enzyme release which was 42% (p = 0.0001) higher than the median release rate of the control group. Patients with persistent coronary occlusion in spite of thrombolytic therapy had a median infarct size which was 11% (NS) higher than the median infarct size of the control group, although the median rate of enzyme release was still 23% (p = 0.02) higher than the median release rate of the control group. It is concluded that thrombolysis in the early phase of AMI limits infarct size and that intracoronary SK treatment itself accelerates the process of enzyme release from infarcted myocardium, independent of the angiographic result.

Right after the first signs and symptoms of acute myocardial infarctions the prognosis is determined by the interventions which are carried out at that time. Preservation of as much myocardial tissue is the key element. Early deobstruction and reperfusion of the myocardium at jeopardy can lead to limitation of the ultimate infarct size, improved ventricular function and a halving of the 1-year mortality. Early supportive therapy with beta-blockade and calcium antagonists may enhance this effect. Data in 533 patients randomized to either a reperfusion strategy or to conventional therapy, combined with those from the recent literature on thrombolysis and early beta-blockade, provide the basis for this point of view. Once infarction is unavoidable and in the process of completion, probably 3-4 h after onset of symptoms, only supportive therapy is recommended, which will hardly change the outcome except for interventions during clinical care such as defibrillation. In 351 other survivors of myocardial infarction the value of clinical variables, a symptom-limited bicycle stress test at discharge, radionuclide ventriculography and 24-hour ambulatory electrocardiogram was compared in predicting 1-year survival. A history of previous myocardial infarction and heart failure during the current episode proved to be the strongest clinical predictors of death. Similarly, a low ejection fraction (less than 40%) and an insufficient blood pressure rise during stress testing (less than 30 mm Hg) identified a high risk group. Stress-test-induced angina and ST depression as well as ventricular arrhythmias from 24-hour electrocardiography were less good as predictors. In these patients treatment should be individualized and may require arteriography. Patients eligible for and completing a normal bicycle stress test after myocardial infarction proved to be a low risk group, which may constitute 65% of the total, seen in tertiary referral centers and even more in community hospitals. They neither require therapy nor further investigation. A subgroup with an intermediate risk can be identified when clinical variables, stress testing and/or resting radionuclide ventriculography are abnormal. This group requires 'tailored' therapy. Therefore, after infarction recovery, we recommend a pre-discharge stress test routinely to complement the clinical evaluation, since it also provides information on physical capacity, the indication of arrhythmias and the presence of myocardial ischemia. Thus, optimal management of acute myocardial infarction requires a stratified approach, which does not require expensive testing procedures.

The value of an exercise test, as well as any other diagnostic procedure, is dependent on the quality of the test itself as well as the knowledge of the physician who ordered the test. The indications for the test should be clear, while the physician should be able to correlate the test results with other information on the patient.

The very existence of several methods (6, 13, 16, 20, 26, 41) to analyze left ventricular wall motion from contrast angiograms indicates that no exact, generally accepted procedure is available to track fixed points along the endocardial wall. In animals, specific sites of the endocardium can easily be followed with endocardially implanted metal clips (5, 32, 44) and roentgen cinematography. For obvious reasons, endocardial markers have not been inserted in humans, although midwall motion (9) and epicardial wall motion (3, 15, 31) have been studied in human hearts with surgically implanted metal markers. However, major differences exist in extent and direction of movements of neighboring endocardial, midwall and epicardial sites as the wall thickens (44, 64). Therefore, none of these methods can provide an accurate description of endocardial wall motion. Recently, we described and evaluated a method to assess left ventricular endocardial wall motion in humans from the pathways of anatomic landmarks recognizable on the endocardial border. For delineation of the endocardial border in the contrast angiogram, an automated high resolution outlining system (60) was employed. In the detected left ventricular contour, small landmarks are available that can be followed throughout the cardiac cycle by analysis of consecutive frames of the cineangiogram. The hypothesis that these landmarks represent specific anatomic sites has been validated by placing minute “harpoons” in the endocardium of piglets.

QT-interval prolongation is a recognized risk indicator for ventricular arrhythmias and sudden cardiac death. The effect of beta-blockers on the change of the QT-interval relative to the change in heart rate was studied in 269 male patients who underwent computer-interpreted exercise tests. None of the patients studied used anti-arrhythmic drugs, diuretics or digoxin. In 141 men on beta-blockers the relation between Q-peakT interval and heart rate could be described as follows: Q-peakT = -1.48 X heart rate + 415. In 128 patients not on beta-blockers this relation was: Q-peakT = -1.14 X heart rate + 379. The difference of the slopes is 0.34 (0.22 - 0.46, 95% confidence interval). This difference was even more pronounced in a subgroup of coronary patients: 0.44 (0.30 - 0.57, 95% confidence interval). These results indicate that in men using beta-blockers the QT-interval shortens faster with increasing heart rate than in men not using them. At high heart rates patients on beta-blockers have a shorter QT-interval than those not using them. These observations could explain the beneficial effect of beta-blockers on exercise-induced ventricular arrhythmias and sudden death in coronary patients.

The imidazol-pyridine ARL-115 BS (sulmazol) has both positive inotropic and vasodilatory effects. Its hemodynamic effects were studied in 13 patients with shock after myocardial infarction. All patients required dobutamine or dopamine, while nine were treated with intra-aortic balloon counterpulsation. After a loading dose of 50 mg, sulmazol was administered at 50 mg/h followed by 100 mg/h during 30 or 60 minutes. At the highest dose of sulmazol, cardiac output increased from 4.3 +/- 1.1 to 4.9 +/- 1.5 1/min; systemic vascular resistance decreased from 1405 +/- 473 to 1228 +/- 439 dynes . s . cm-5, while pulmonary capillary wedge pressure decreased from 22 +/- 6 to 17 +/- 7 mm Hg. No changes occurred in heart rate or mean arterial pressure. The effect of sulmazol was greater than the effect of an increased dosage of dobutamine in five patients in whom this was studied. Episodes of supraventricular tachycardia occurred in two patients. No other side effects were observed. The hemodynamic changes caused by sulmazol favour its use in the treatment of acute cardiac failure, and cardiogenic shock.

The diagnostic accuracy of conventional exercise electrocardiography was compared with exercise algorithms specifically aimed at application in females, with R wave and heart rate adjusted ST-segment changes, and with discriminant analysis. A symptom-limited bicycle exercise test was performed by 189 females without previous infarction with a normal electrocardiogram (ECG) at rest. Frank lead ECG was computer processed. ST-segment amplitudes in lead X were superior to measurements in lead Y, but their sensitivity amounted only to 50% at a specificity of 90%. Correction for R wave amplitude marginally increased sensitivity. It was confirmed that leads with inferiorly directed vectors such as standard leads II, III, aVF or Frank lead Y should not be used for diagnostic purposes in females. Exercise-induced increases in R-wave amplitude of at least 0.1 mV occurred in only 8% of females with coronary disease. Previously described discriminant function using attained heart rate, ST-segment depression and a sex-dependent ST segment correction factor yielded a sensitivity of 60% at a specificity of 90%. Sensitivities of heart rate adjusted ST-segment changes and of a previously proposed discriminant function were greater than 70% at a specificity of 90%. It is concluded that the diagnostic yield of exercise testing in females can be improved by use of more sophisticated electrocardiographic and exercise variables.

In 1979, a new form was introduced which was based on an optical mark sense card. This form extended the traditional written patient records with coded information [l]. The coded data was fed into the Thoraxcentrum Utility System (TUS) [2]. The mark sense cards were collected every week and placed in an optical mark reader by a computer operator. Initial experience with the scheme was encouraging, since most of the forms were completed. In 1980, and again in 1982, the form was revised and extended as part of a joint project with the Netherlands Interuniversity Cardiology Institute. A check in 1981, however, showed missing forms for 17% of the patients and many inconsistencies in the data. A major cause appeared to be lack of motivation among the CCU physicians, probably due to a lack of feedback from the system. The off-line nature of the system made it hard to correct inconsistencies or omissions. In order to overcome these problems, an extension to the TUS CCU module was developed to provide a discharge letter based on a summary of the coded information and mostly generated by the computer. When the patient leaves the CCU the letter is produced and can be sent immediately to the general practitioner or to the specialist (figure 1).

The attempt to salvage myocardium threatened by ischemia during temporary or permanent occlusion of one or more of the nutrient arteries, is based on the observation that the major determinant of survival is the extent to which myocardium has been lost through infarction. Modern clinical cardiology has therefore looked at various approaches which might limit unnecessary loss of potentially viable myocardium. These are attempts to reduce the oxygen consumption through pharmacological means, attempts at restoring the blood supply and oxygen delivery at an early stage by manipulations on the coronary arteries and interventions aimed at "protecting" cardiac cells threatened by ischemia or reperfusion. Endpoints considered to be proof of improved left ventricular function will be wall motion and ejection fraction measurements as well as reduction in death rate and other serious cardiovascular complications. Although final proof from prospective randomized studies, one of which is carried out at this institution with intracoronary streptokinase in over 300 patients, will not be available at the time of this presentation, arguments will be provided which indicate that restoration of blood supply at an early stage, preferably supported by pharmacological therapy with beta-blockade and calcium antagonists, is to be preferred inasmuch as current data indicate improved function, and in certain subsets, improved life expectancy.

The activity of alpha-hydroxybutyrate dehydrogenase, creatine kinase, creatine kinase MB and aspartate aminotransferase was measured on serial plasma samples from patients with acute myocardial infarction. The study was part of a multicentre randomised trial of the effect of thrombolytic treatment in the acute phase of acute myocardial infarction. The applicability and comparability of enzyme tests for the estimation of myocardial injury were studied in 76 control patients and 74 patients treated with streptokinase. Treatment with streptokinase caused a considerable acceleration of enzyme release after acute myocardial infarction, both in patients with persistent coronary occlusion and in those with successful reperfusion. But this changed pattern of enzyme release did not affect the rate of enzyme elimination from plasma or the released proportions of different enzymes. Thus the assessment of infarct size by measurement of these enzyme activities can also be applied to patients treated with streptokinase. Moreover, the enzymes measured in the present study are all equally valid markers of myocardial injury.

Nifedipine is a strong calcium antagonist; it blocks the excitation-contraction coupling, yet at therapeutic dosage levels it has few side effects. It is said that a single molecule of nifedipine can neutralize the effects of several thousand calcium ions in the excitation-process. Thus this agent reduces the ability of the cardiac cells to develop mechanical tension yet it does not affect electrical excitation. Calcium antagonists are also potent dilators, particularly of the arteries on the periphery of the human body and in the coronary arterial system. The basic mode of action is thought to be the same, i.e. reduction of the calcium transport, this time into the smooth muscle cells of the arterial wall, thus "forcing' the arteriole to dilate. The resultant action is a reduction in afterload, while there is an increase in perfusion of the coronary vascular bed. Thus there is a dual action, the one centrally, the other peripherally both of which will be particularly effective in patients with unstable angina (UA) in whom excess coronary vascular tone is suspected. Beta-blockers, particularly propranolol and metoprolol, with which we have the most experience, work via beta 2 adrenoceptor blockade in the heart. Cardiac frequency decreases, arrhythmias are suppressed, blood pressure may decrease, all reducing cardiac work. If in UA variations in coronary vascular tone and frank spasm do occur then is would be more logical to use Ca-antagonists instead of beta-blockade. Our clinical experience to date has not shown that patients with UA are worsened by propranolol or metoprolol but there are scores of clinical reports showing worsening of chest pain in Prinzmetal's syndrome, presumably because beta-blockade leads to excessive alpha-adrenergic vascular tone. On the other hand, in one year experience with 73 patients with UA, 52 did not experience relief from adequate beta-blockade until nifedipine was added. Within 2 hours, 42 of the 52 became asymptomatic--thus indicating that in UA the need for spasmolytic therapy prevails over the need for beta-blockade. In many cases of UA both drugs may have a place however, their exact relative value remains to be established.

The effect of thrombolysis in acute myocardial infarction on enzymatic infarct size, left ventricular function, and early mortality was studied in subsets of patients in a randomized trial at The Netherlands Interuniversity Cardiological Institute during a 5-year period. Early thrombolytic therapy with intracoronary streptokinase (152 patients) or with intracoronary streptokinase preceded by intravenous streptokinase (117 patients) was compared to conventional treatment (264 patients). All 533 patients were admitted to the coronary care unit within 4 hours after onset of symptoms indicative of acute myocardial infarction. There were 488 patients eligible for this detailed analysis, of whom 245 were allocated for thrombolytic therapy. Early angiography was performed in 212 of the 245 patients. Patency of the infarct-related artery was achieved in 181 patients (85%). Enzymatic infarct size measured from cumulative alpha HBDH release was smaller in patients allocated to thrombolytic therapy (median 760 U/l vs. 1179 U/l in controls, p = 0.0001). LVEF measured by radionuclide angiography before discharge was higher after thrombolytic therapy (median 50% vs. 43% in controls, p = 0.0001). The 12-month mortality was lower in patients allocated to thrombolytic therapy (8% vs. 16% in the control group, p0.01). In multivariate regression analysis, infarct size limitation, improvement of LVEF, and a 3-month mortality were predicted by ST, time from onset of symptoms to admission, and Killip class at admission. Thrombolysis was most useful in patients admitted within 2 hours after onset of symptoms and in patients with ST of 1.2 mV or more. On the other hand, no beneficial effects of streptokinase on enzymatic infarct size, left ventricular function, or mortality were observed in the subset of patients with ST less than 1.2 mV admitted 2 to 4 hours after onset of symptoms. In the long term, improved survival and enhanced quality of life are most evident after thrombolytic therapy in patients with larger anterior wall infarction, and less pronounced in patients with smaller inferior wall infarction.

A total of 533 patients with acute myocardial infarction of less than 4-h duration were enrolled in the multicenter randomized trial of intracoronary thrombolysis compared to conventional treatment. In two of the five participating centers, an additional coronary angioplasty immediately after thrombolysis was attempted in 46 patients. According to the treatment allocation and early and late patency of the infarct related vessel, patients were subdivided into three groups: conventionally treated (group A); successful coronary angioplasty following thrombolysis with persistent patent infarct related vessel (group B); and late patency of the infarct related vessel postthrombolytic therapy without angioplasty (group C). The highest global ejection fractions were observed in group B (54% +/- 10%) and group C (55% +/- 13%), while the lowest ejection fraction was found in group A (47% +/- 14%). The sequential changes in global ejection fraction from the acute to the chronic stage was + 4% (p = 0.05) in group B, while no significant changes could be demonstrated in group C. Furthermore, in the group successfully treated by angioplasty, the improvement in global ejection fraction was more pronounced and persisted up to three months after the intervention. This was supported by analysis of regional myocardial function of the infarct zone (+ 16% improvement, p = 0.01). The long-term clinical follow-up (median 24 months) of the patients successfully treated by combined procedure of thrombolysis and angioplasty (group B) was most favourable with a lower incidence of re-infarction (6%), and late coronary bypass surgery (13%) and/or (re)-percutaneous transluminal coronary angioplasty (3%) was performed less frequently. These results suggest that reperfusion may need to be supplemented by additional revascularization procedures in order to optimize the changes of obtaining full functional recovery and so to improve the prognosis.

To evaluate, during cardiac catheterization, what constitutes a physiologically significant obstruction to blood flow in the human coronary system, computer-based quantitative analysis of coronary angiograms was performed on the angiograms of 31 patients with isolated disease of the proximal left anterior descending coronary artery. The angiographic severity of stenosis was compared with the transstenotic pressure gradient measured with the dilation catheter during angioplasty and with the results of exercise thallium scintigraphy. A curvilinear relationship was found between the pressure gradient across the stenosis (normalized for the mean aortic pressure) and the residual minimal area of obstruction (after subtracting the area of the angioplasty catheter). This relationship was best fitted by the equation: normalized mean pressure gradient = a + b . log [obstruction area], r = .74. The measurements of the percent area of stenosis (cutoff 80%) and of the transstenotic pressure gradient (cutoff 0.30) obtained at rest correctly predicted the occurrence of thallium perfusion defects induced by exercise in 83% of the patients.

Heart transplantation candidates frequently have a disturbed liver function. Two cases with jaundice are described in whom the cause and prognosis of the associated liver disease were analysed. In the 4-yr period during which heart transplantation patients with a disturbed liver function were investigated, "cirrose cardiaque" was not encountered; liver tests usually normalized after a successful heart transplant.

In recent years, computer programs have been developed to assist in the exercise laboratory. The aims of such computer systems may include (a) improvement of the ECG interpretation; (b) improved standardization of the test procedure; (c) reduction of the technical tasks of the physician and the technician who supervise the test, such as control of the ECG writer and the bicycle ergometer; and (d) generation of a report of the test. At the Thoraxcenter such a system has been in routine use since 1977 [19]. Other systems have been developed in other laboratories [1, 6–9, 11, 18]. However, most of these do not perform all tasks listed above [1, 6, 8, 11, 18].