A Mechanized Pediatric Elbow Joint Powered by a De-Based Artificial Skeletal Muscle.

To increase the acceptability of exoskeletons, there is growing attention toward finding an alternative soft actuator that can safely perform at close vicinity of the human body. In this study, we investigated the capability of the dielectric elastomer actuators (DEAs), for muscle-like actuation of rehabilitation robots. First, an artificial skeletal muscle was configured using commercially available stacked DEAs arranged in a 3x4 array of three parallel fibers consisting of four DEAs connected in series. The shortening and force generation capabilities of this artificial muscle were then measured. An alternate 3x5 version of this muscle was mounted on the forearm of an upper extremity phantom model to actuate its elbow joint. The actuation capability of this muscle was then tested under various tensile loads, 1 N to 4 N, placed at the center of mass of the forearm+hand of the phantom model. The active range of motion and angular velocity of the phantom model's tip of the hand were measured using a motion capture system. The 3×4 artificial muscle produced 30.47 N of force and 5.3 mm of maximum shortening. The 3x5 artificial muscle was capable of actuating the elbow flexion 19.5º with 16.2 º/s angular velocity in the sagittal plane, under a 1 N tensile load. The active range of motion was substantially reduced as the tensile loads increased, which limits the capability of these muscles in the current upper extremity exoskeleton design.

Coronary patency after intravenous infusion of recombinant tissue-type plasminogen activator in acute myocardial infarction.

The relation between coronary patency after infusion of recombinant tissue-type plasminogen activator (rt-PA) and clinical and laboratory findings was assessed in patients with acute myocardial infarction. This study focused primarily on information available early in the hospitalization phase. Data were available for 243 patients who received the full dose of rt-PA and who had assessable coronary angiograms 90 min after the start of the intravenous infusion. The infarct-related vessel was scored by an independent assessment committee as being patent in 65% of patients. The left anterior descending coronary artery was involved in 53% of patients, and proximal localization of the infarct-related vessel occurred in 65%. In the majority of patients (85%), the infusion was started within 4 h of the acute event. Neither the angiographic location of the infarct-related vessel nor electrocardiographic evidence of infarct severity or location appeared to have a bearing on thrombolysis with rt-PA. Multivariate logistic regression analysis identified three independent predictors of coronary patency: hematocrit 43 to 47%, blood plasminogen level greater than or equal to 90% of normal and serum alkaline phosphatase greater than or equal to 82% of the local upper normal limit. In addition, the use of intravenous nitrates suggests a positive association with patency.

Relative value of clinical variables, bicycle ergometry, rest radionuclide ventriculography and 24 hour ambulatory electrocardiographic monitoring at discharge to predict 1 year survival after myocardial infarction.

The relative value of predischarge clinical variables, bicycle ergometry, radionuclide ventriculography and 24 hour ambulatory electrocardiographic monitoring for predicting survival during the first year in 351 hospital survivors of acute myocardial infarction was assessed. Discriminant function analysis showed that in patients eligible for stress testing the extent of blood pressure increase during exercise slightly improved the predictive accuracy beyond that of simple clinical variables (history of previous myocardial infarction, persistent heart failure after the acute phase of infarction and use of digitalis at discharge), whereas radionuclide ventriculography and 24 hour electrocardiographic monitoring did not. The predictive value for mortality was 12% with clinical variables alone and 15% with the stress test added. Radionuclide ventriculography and 24 hour electrocardiographic monitoring were slightly additive to clinical information in the whole group of patients independent of the eligibility for stress testing (predictive value for mortality 24% with clinical variables alone and 26% with radionuclide ejection fraction and 24 hour electrocardiographic monitoring added). It is concluded that the appropriate use of simple clinical variables and stress testing is sufficient for risk stratification in postinfarction patients, whereas radionuclide ventriculography and 24 hour electrocardiographic monitoring should be limited to patients not eligible for stress testing.

Reasons for the lack of benefit of immediate angioplasty during recombinant tissue plasminogen activator therapy for acute myocardial infarction: a regional wall motion analysis. European Cooperative Study Group.

Regional ventricular wall motion analysis utilizing three different methods was performed on predischarge left ventriculograms from 291 of 367 patients enrolled in a randomized trial of single chain recombinant tissue-type plasminogen activator (rt-PA), aspirin and heparin with and without immediate angioplasty in patients with acute myocardial infarction. With univariate analysis, no difference in regional wall motion variables between the two treatment groups was observed. However, with individual baseline risk assessment by multivariate linear regression analysis using baseline characteristics known to be related to left ventricular function after thrombolytic therapy or outcome of coronary angioplasty, or both, an excess of high risk patients in the invasive treatment group was detected. To adjust for this unequal distribution of baseline risk, multivariate linear regression analysis was performed. No benefit of immediate coronary angioplasty was observed after adjustment. Reocclusion or reinfarction, or both, occurred more frequently in the invasive than in the noninvasive treatment group (18% versus 13%, respectively). Among patients with a patent infarct-related vessel on angiography between days 10 and 22 and without reinfarction before angiography, there was a trend toward benefit from the invasive strategy, indicating that reocclusion and reinfarction might be responsible for the lack of benefit of the invasive strategy. This implies that immediate coronary angioplasty may be beneficial in selected patients, provided that these complications can be prevented.

Increased serum levels of fibrinogen degradation products due to treatment with recombinant tissue-type plasminogen activator for acute myocardial infarction are related to bleeding complications, but not to coronary patency. European Co-operative Study Groups for rt-PA.

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)

Treatment of angina pectoris: associations with symptom severity.

OBJECTIVE: To evaluate whether the frequency of anginal attacks in medically treated patients with stable angina is related to the intensity of anti-anginal treatment, the clinical history and coronary anatomy. METHODS: Analysis of baseline data from the A Coronary disease Trial Investigating Outcome with Nifedipine GITS (ACTION) study, an ongoing placebo-controlled trial in 7669 patients with stable angina pectoris who require anti-anginal treatment. RESULTS: Prior to randomisation, 8% of 7669 patients had no anginal attacks, 63% had occasional, 22% had regular, 4% had frequent and 3% had daily attacks. Men (79% of all patients) and patients with a history of MI (51%) had less frequent anginal attacks (P<0.0001). The number of coronary angiograms ever performed (70% had at least one angiogram), the extent of angiographic coronary disease (32% of those who had angiography had more than two-vessel disease), a history of peripheral artery disease (12%), the number of anti-anginal drugs used (64% were prescribed two or more such medications) and a history of revascularisation (a history of coronary bypass surgery was present in 23% and of balloon dilatation in 26%) were each positively associated with anginal attack frequency. CONCLUSIONS: For the majority of patients with chronic stable angina not on a calcium-antagonist, medical treatment with other anti-anginal drugs is sufficient to control symptoms and only a minority of patients are refractory to medical treatment. Invasive treatments for chronic stable angina are only needed in a small proportion where symptoms persist.

Does drug treatment improve survival? Reconciling the trials in mild-to-moderate hypertension.

OBJECTIVE: To evaluate whether drug treatment for mild-to-moderate hypertension in middle-aged patients improves survival and to study how the conflicting results of individual trials may be explained. STUDY SELECTION: A meta-analysis was performed, including seven randomized trials in mild-to-moderate hypertensive (diastolic blood pressure 90-114 mmHg) middle-aged patients. DATA EXTRACTION: A comparison was made between all-cause mortality and fatal coronary heart disease and stroke in the intervention and control group of the individual trials, using a method of meta-analysis based on weighted linear regression. RESULTS: In trials with a high all-cause mortality rate (> 6 per 1000 patient-years) in the control group, antihypertensive drug treatment increased life expectancy. When all-cause mortality in the control group was low, treatment showed no effect or even an opposite effect. Findings on mortality from coronary heart disease were similar, whereas drug treatment decreased stroke mortality irrespective of the incidence of stroke in the control group. CONCLUSIONS: Drug treatment for mild-to-moderate hypertension in middle-aged patients may reduce all-cause mortality and the risk of fatal coronary events when treatment is initiated in those beyond a certain baseline mortality risk. Drug treatment in hypertensive patients at a lower mortality risk has no influence on or may even increase mortality.

Monitoring methods, considerations, and statement of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) Ethical Review Committee.

The Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) was terminated prematurely when an independent Ethical Review Committee concluded, on the basis of interim analyses, that continuation would not be advisable on either ethical or scientific grounds. Among 124 patients treated with enalapril and 120 randomized to placebo, 6-month mortality rates were 27 and 48%, respectively. The 2 groups were found to be well balanced with regard to baseline clinical characteristics, and a consistent treatment effect was evident among subgroups. Furthermore, the difference favoring enalapril was found to have been present since the beginning of the study and was consistent over time. Based on these findings, the study was halted on December 14, 1986.

Efficacy of nifedipine and metoprolol in the early treatment of unstable angina in the coronary care unit: findings from the Holland Interuniversity Nifedipine/metoprolol Trial (HINT).

A multicenter, double-blind, placebo-controlled, randomized trial of nifedipine, metoprolol and their combination was conducted in 338 patients with unstable angina (hospital admission diagnosis) who had not previously received treatment with a beta blocker. In addition, nifedipine was compared with placebo in 177 patients who were receiving beta blockers upon hospital admission. The main outcome event was the recurrence of ischemia or progression to myocardial infarction within 48 hours. Trial medication effects are expressed as ratios of event rates relative to placebo, e.g., for nifedipine as the event rate under nifedipine divided by that under placebo; 95% confidence intervals are also given. In patients not pretreated with a beta blocker the rate ratio for nifedipine was 1.15 (0.83, 1.64), for metoprolol 0.76 (0.49, 1.16) and for the combination 0.80 (0.53, 1.19). In patients already receiving a beta blocker, the addition of nifedipine was favorable and the rate ratio was 0.68 (0.47, 0.97). Equal numbers of patients developed myocardial infarction and reversible ischemia. Most infarctions occurred early, within 6 hours of randomization. In patients who were not already taking a beta blocker, the nifedipine rate ratio for infarction only was 1.51 (0.87, 2.74). These results suggest that, in patients not previously receiving beta blockers, metoprolol has a beneficial short-term effect on unstable angina, that a fixed combination with nifedipine provides no further gain and that nifedipine may be ineffective or counterproductive. On the other hand, the addition of nifedipine to existing beta blockade when the patient becomes unstable seems beneficial.

Meta-analysis of morbidity and mortality in five exercise capacity trials evaluating ramipril in chronic congestive cardiac failure.

In 5 separate exercise capacity trials in similar patients with chronic congestive heart failure performed in Europe, the United States, and South Africa, 627 patients were randomized to ramipril and 428 to placebo. The dose of ramipril ranged from 1.25 to 20 mg/day. Follow-up was at 12 or 24 weeks. None of the trials were designed to assess efficacy with regard to clinical outcome. To assess in the combined experience whether there was an effect of ramipril on mortality, hospitalization, functional classification (New York Heart Association class), and exercise capacity, we pooled data from each trial and performed a mata-analysis. Of the patients randomized to ramipril and placebo, respectively, and based on intention to treat, 14 (2.2%) and 18 (3.8%) patients died (odds ratio 0.60, 95% confidence interval 0.28 to 1.29), and 59 (9.4%) and 67 (14.3%) patients died or were hospitalized (odds ratio 0.68, 95% confidence interval 0.46 to 1.00). The New York Heart Association class improved in 29% and 25% respectively, whereas 8% and 15% deteriorated (p=0.04, based on intention to treat; death and hospitalization considered as deterioration). In ranked comparisons based on intention to treat and with imputation of exercise time as 0 for patients who were unable to exercise because of death or who were hospitalized, exercise capacity was significantly improved by rampril. We concluded that rampiril is likely to have an effect on mortality, morbidity, and functional capacity in patients with chronic congestive heart failure similar to that of other angiotensin-converting enzyme inhibitors.

Left ventricular systolic and diastolic function, and exercise capacity six to eight weeks after acute myocardial infarction. The DEFIANT Study Group. Doppler Flow and Echocardiography in Functional Cardiac Insufficiency: Assessment of Nisoldipine Therapy.

Echocardiographic and Doppler-derived measurements of left ventricular (LV) function at rest were examined as predictors of maximal bicycle exercise capacity in a homogeneous group of 115 patients with mild to moderate LV dysfunction (ejection fraction 22 to 56%, median 43%) participating in the DEFIANT study of nisoldipine after acute myocardial infarction. Although the relations were not exact, peak exercise work load 7 weeks after infarction correlated with measurements of diastolic LV function at rest. Exercise work load was inversely related to peak late diastolic transmitral blood flow velocity (A wave) (slope -86.6; 95% confidence interval -120.9 to -52.2) and directly to the E/A ratio (slope 20.5; 95% confidence interval 6.0 to 35.1). The relations between exercise work load and peak late diastolic flow velocity remained significant after correction for age, sex, heart rate at rest, and use of beta-blocking drugs or nisoldipine. There was no relation between peak exercise work load and peak early diastolic transmitral flow velocity (E wave), isovolumic relaxation period or deceleration time. Measurements of systolic LV function (LV end-diastolic and end-systolic volumes, and ejection fraction, stroke volume and cardiac index) were also not significant as predictors of exercise capacity.

Effects of nifedipine on left ventricular performance in unstable angina pectoris during a follow-up of 48 hours.

In 1981, a large, double-blind, randomized, multicenter trial was started in The Netherlands to evaluate the therapeutic effects of nifedipine or metoprolol in patients with unstable angina. This study, called the Holland Interuniversity Nifedipine Trial (HINT), included several hundred patients to establish potential therapeutic effects. From December 1982 until January 1984 the effects of nifedipine on left ventricular (LV) performance in a subgroup of 37 HINT patients were studied using radionuclide techniques. All patients (18 treated with nifedipine, 19 with placebo) underwent radionuclide angiography and 33 underwent thallium-201 scintigraphy just before and 48 hours after the start of treatment with the experimental medication. Radionuclide angiographic studies were also performed 1 hour (29 patients) and 4 hours (31 patients) after the start of treatment. The thallium-201 images showed defects in 24 (73%) of the baseline images and in 21 (64%) of the 48-hour images. No significant differences were seen between patients receiving nifedipine or placebo in the incidence of new defects or in the disappearance of defects at 48 hours. Changes in thallium-201 images were not related to recurrence of myocardial ischemia or the development of acute myocardial infarction. Nineteen of the 37 patients (51%) with baseline blood pool images had a reduced LV ejection fraction (EF) (38 +/- 10%) and 18 patients (49%) had a normal LVEF of 56 +/- 5%. LVEF improved after 48 hours in 8 patients receiving nifedipine and in only 1 patient receiving placebo (p less than 0.02). This effect was not present at 1 and 4 hours after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute coronary thrombolysis with recombinant human tissue-type plasminogen activator: initial patency and influence of maintained infusion on reocclusion rate.

An intravenous infusion of 40 mg of recombinant tissue-type plasminogen activator (rt-PA) was given intravenously over 90 minutes to 123 patients with acute myocardial infarction (AMI) of less than 4 hours' duration. A coronary angiogram was recorded at the end of the infusion in 119 patients. Central assessment of the angiograms revealed a patent infarct-related artery in 78 patients (patency rate 66%, 95% confidence limits 57 to 74%). Patients with a patent infarct-related artery at the first angiogram were randomized in a double-blind manner to receive a subsequent 6-hour infusion of either 30 mg of rt-PA or placebo. All patients had received an initial bolus of 5,000 IU of heparin and then 1,000 IU/hour until a second angiogram was recorded 6 to 24 hours after the start of the second perfusion. At central assessment of the second coronary angiogram the reocclusion rate was 2 of 36 patients who received rt-PA at the second infusion and 3 of 37 patients not receiving this drug (or the 2 groups combined 7%, 95% confidence limits 2 to 15%). Three of 60 patients (5%, 95% confidence limits 1 to 14%) with patent arteries on both previous angiograms had a later occlusion as judged on the angiogram recorded at hospital discharge. No difference in late reocclusion rates between the 2 treatment groups was observed.

Exercise testing as outcome in congestive heart failure trials. Design considerations when interpreting results.

In addition to standard features of clinical trial design such as randomisation and double-blinding, sensitivity to drug effects is an important consideration when conducting exercise capacity trials in patients with heart failure. Two issues need to be addressed in this context. Firstly, it is important to enrol patients who are potential responders. Patients who have, for their age and sex, normal exercise capacity are unlikely to improve, even when given a drug that has a positive effect on exercise capacity. In addition, those patients who remain clinically stable following withdrawal of their previous drug therapy are unlikely to respond subsequently to an experimental drug with a similar mechanism of action. Secondly, failure to complete scheduled exercise tests during follow-up, prompting a 'per-protocol' analysis of results, may mask the drug's actual effect. To avoid this, an 'intention-to-treat' approach to data collection and analysis, with appropriate allowance made for missing test data, should be adopted.

Do non-potassium-sparing diuretics increase the risk of sudden cardiac death in hypertensive patients? Recent evidence.

Whether non-potassium-sparing diuretics (NPSD) increase the risk of sudden cardiac death in hypertensive patients has been vigorously debated. Diuretic-induced potassium or magnesium depletion leading to cardiac arrhythmias has been suggested as the underlying mechanism. A clear dose-response relationship between NPSD and the reduction in serum K+ exists. Data regarding serum Mg++ and intracellular K+ and Mg++ are too limited to allow conclusions. NPSD seem to increase the risk of ventricular arrhythmias among hypertensive patients with clinical evidence of heart disease, but the number of studies is small. The findings among patients without evidence of heart disease are less conclusive. The interpretation of the studies on electrolyte changes and arrhythmias following diuretic therapy is obscured by the fact that only a minority of studies included a randomly allocated placebo-treated control group. The large hypertension trials provide the strongest evidence that NPSD for hypertension may induce sudden death. Although blood pressure lowering may be expected to reduce the incidence of sudden cardiac death, the incidence in the NPSD group is similar to or even higher than that in the control group in 9 of 10 trials. We conclude that the beneficial effect of NPSD therapy for hypertension is partly offset by an excess risk of sudden death. Thus, alternative drugs, notably potassium-sparing diuretics or beta-blockers, could be preferred as antihypertensive drugs of first choice, although the efficacy of beta-blockers in older patients has recently been challenged.

Sudden cardiac death in patients with hypertension. An association with diuretics and beta-blockers?

The cornerstones of current antihypertensive treatment are diuretics and beta-blockers and the efficacy of these drugs in preventing cardiovascular disease is undisputed. This article focuses on the effect of these 2 drug classes on the incidence of sudden death. Numerous studies have shown that thiazide diuretics have a strong, dosage-dependent potassium-depleting effect, and it has been postulated that this may explain why the reduction in risk of coronary heart disease, observed in hypertension trials, was less pronounced than expected. In 7 trials that included sudden death as an end-point; a pooled risk-ratio of sudden death of 1.5 (95% confidence interval 1.1 to 2.0) was observed when non-potassium-sparing diuretics were compared with placebo. Two recent case-control studies have also strongly indicated that the use of thiazides increases the risk of sudden death. Evidence from trials using potassium-sparing diuretic combinations suggests that these may be better tolerated than thiazide monotherapy. Although it was suggested in the 2 recent case-control studies that recipients of beta-blockers are also at an increased risk of sudden death, further studies are required to confirm this finding, particularly since these drugs have several well-documented cardioprotective effects.

Heart failure treatments: issues of safety versus issues of quality of life.

Congestive heart failure is an important cause of morbidity and mortality in western countries. The profound impact that congestive heart failure has on life expectancy and quality of life has been a continuous stimulus for the development of new drugs for the treatment of this condition. Despite favourable effects on (aspects of) quality of life in short term studies, several of these new agents have been shown to reduce survival in mortality trials. However, patients with severe congestive heart failure may experience such incapacitating symptoms that the question should be raised as to whether an improvement in quality of life makes the increased risk of mortality associated with these new agents acceptable. Drugs which improve quality of life at the expense of an increased risk of mortality can be of value in the treatment of patients with severe congestive heart failure. However, this is only the case if the probability of improvement in quality of life and prolongation of life expectancy for those using the drug exceeds the probability of improvement in quality of life and prolongation of life expectancy for those not using the drug. Unfortunately, most clinical trials in which both mortality and quality of life are evaluated fail to provide information on this composite probability. Despite disappointing results of some recent mortality trials on new pharmacological treatments of congestive heart failure, sound and well designed clinical trials on innovative heart failure treatments in which these composite probabilities are also assessed should be carried out.

Effect of pimobendan on exercise capacity in patients with heart failure: main results from the Pimobendan in Congestive Heart Failure (PICO) trial.

PRIMARY OBJECTIVE: To determine the effects of pimobendan 2.5 and 5 mg daily on exercise capacity in patients with chronic heart failure. DESIGN: A randomised, double blind, placebo controlled trial of the addition of pimobendan to conventional treatment with a minimum follow up of 24 weeks. SETTING: Outpatient cardiology clinics in six European countries. PATIENTS: 317 patients with stable symptomatic heart failure, objectively impaired exercise capacity, and an ejection fraction of 45% or lower who were treated with at least an angiotensin converting enzyme inhibitor and a diuretic and who tolerated a test dose of pimobendan. RESULTS: Compared with placebo, both pimobendan 2.5 and 5 mg daily improved exercise duration (bicycle ergometry) by 6% (P = 0.03 and 0.05) after 24 weeks of treatment. At that time 63% of patients allocated to pimobendan and 59% of those allocated to placebo were alive and able to exercise to at least the same level as at entry (P = 0.5). No significant effects on oxygen consumption (assessed in a subgroup of patients) and on quality of life (assessed by questionnaire) were observed. Pimobendan was well tolerated. Proarrhythmic effects (24-hour electrocardiography) were not observed. In both pimobendan groups combined the hazard of death was 1.8 (95% confidence interval 0.9 to 3.5) times higher than in the placebo group. CONCLUSIONS: Pimobendan improves exercise capacity in patients with chronic heart failure who are also on conventional treatment. The balance between benefit and risk of treatment with this compound remains to be established however.

Left ventricular performance in unstable angina: assessment with radionuclide techniques.

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.

Improved prognosis during and after myocardial infarction: a plea for an integrated and stratified approach.

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)